Category: 8. Health

New evidence urges caution with TMP-SMX antibiotics in early pregnancy, highlighting safer options for treating urinary tract infections.

Study: First-Trimester Antibiotic Use for Urinary Tract Infection and Risk of Congenital Malformations. Image Credit: HenadziPechan / Shutterstock

In a recent study published in JAMA Network Open, researchers evaluated the risk of congenital malformations following antibiotic treatment for urinary tract infection (UTI) during the first trimester of pregnancy.

UTIs, such as acute cystitis and asymptomatic bacteriuria (ASB), are common in pregnancy and are associated with adverse outcomes, including low birth weight, preterm birth, maternal sepsis, and pyelonephritis. Routine ASB screening is recommended at the initial prenatal visit, often leading to antibiotic therapy in the first trimester.

However, studies have raised concerns about higher risks of congenital malformations associated with two antibiotics used for UTI treatment: trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin, albeit these studies have significant methodological limitations. Therefore, evidence on the safety of antibiotics in pregnancy is necessary to guide clinical practice.

About the study

In the present study, researchers investigated whether TMP-SMX, fluoroquinolones, and nitrofurantoin were associated with congenital malformations compared to other antibiotics used for UTI treatment in the United States (US). First, pregnant individuals aged 15–49 receiving antibiotics for UTI in their first trimester and their live-born infants were identified from a commercially insured population between 2006 and 2022.

Individuals receiving more than one UTI-related antibiotic, those with a spinal cord injury, immunosuppression, chromosomal abnormalities, and pregnant women exposed to a teratogenic medication in the first trimester were excluded. Outpatient pharmacy claims were used to identify antibiotics dispensed for UTI treatment, which included TMP-SMX, nitrofurantoin, β-lactams, and fluoroquinolones (ofloxacin, ciprofloxacin, and levofloxacin).

β-lactams were used as the reference, as these agents are deemed safe in pregnancy. The study’s outcomes were congenital malformations that were identified using validated claims-based algorithms adapted from Kharbanda et al. Log-binomial regression models assessed the association between antibiotics and malformation risk. Potential confounders included demographic characteristics, concomitant medication, comorbidities, and healthcare utilization measures.

Further, numerous sensitivity analyses were performed to evaluate the robustness of findings. These included restricting the reference group to cephalexin or amoxicillin, using an alternative outcome definition, and restricting the cohort to symptomatic UTI. The team also explored gestational timing effects by narrowing exposure windows to critical organogenesis periods (e.g., 4-9 weeks for cardiac defects). Finally, the team examined associations between antibiotics and the risk of cardiac malformations and any malformations in a larger cohort of pregnant individuals receiving UTI-related antibiotics for any indication.

Findings

The study included 71,604 pregnancies, with 59.2% exposed to nitrofurantoin, 30.8% exposed to β-lactams, 5.1% exposed to fluoroquinolones, and 4.9% exposed to TMP-SMX for UTI treatment in their first trimester. Median gestational age at antibiotic exposure differed significantly: TMP-SMX and fluoroquinolones were prescribed earlier (26 and 18 days post-LMP, respectively) than β-lactams or nitrofurantoin (63 and 62 days). In total, 1,518 infants were identified with congenital malformations. The absolute, unadjusted risk of any congenital malformation was 19.8, 21.2, 23.5, and 26.9 per 1,000 infants for β-lactams, nitrofurantoin, fluoroquinolones, and TMP-SMX, respectively. Estimates were similar for cardiac malformations.

The median (IQR) gestational age at index for symptomatic UTI was 6 (3-9) weeks compared with 9 (7-11) weeks for asymptomatic bacteriuria. TMP-SMX indicates trimethoprim-sulfamethoxazole.

Infants exposed to TMP-SMX had an increased risk of any malformation compared to those exposed to β-lactams (adjusted RR 1.35; 95% CI 1.04-1.75). The researchers estimated that one additional malformation would occur for every 145 pregnancies exposed to TMP-SMX. The malformation risk was similar for infants exposed to fluoroquinolones or nitrofurantoin compared to those exposed to β-lactams.

In organ-specific malformation analyses, there was a similar risk for cardiac malformations for β-lactam- and TMP-SMX-exposed pregnancies, but TMP-SMX was associated with increased relative risk for orofacial/respiratory malformations (RR 2.89; 95% CI 1.31-6.41) and specifically for severe cardiac defects (RR 2.09), other cardiac defects (RR 1.52), and cleft lip/palate (RR 3.23). However, risk difference estimates for these specific malformations included the null value, indicating uncertainty in absolute risk.

In sensitivity analyses:

• Alternative outcome definitions and reference groups yielded consistent results.
• Restricting to symptomatic UTIs (excluding ASB) did not meaningfully change effect estimates.
• Analyses accounting for gestational timing showed TMP-SMX risk persisted but became less precise when narrowed to organogenesis windows.

Finally, the larger cohort included 256,686 pregnant individuals receiving UTI antibiotics for any indication. This alternative analysis was specifically designed to address potential confounding by indication. In this cohort, the risk of any malformation was higher among pregnancies exposed to TMP-SMX specifically for UTI than for other indications. The risk did not vary by indication for other antibiotics. Further, the risk for cardiac malformations or any malformations was similar for infants exposed to fluoroquinolones, TMP-SMX, or nitrofurantoin compared to those exposed to β-lactams. However, analyses for fluoroquinolones were limited by smaller sample sizes (n=3,663), resulting in wider confidence intervals and less precise estimates.

Conclusions

Together, TMP-SMX exposure for UTI treatment in the first trimester was associated with a higher risk of any congenital malformation. It was also associated with an increased relative risk (though uncertain absolute risk) for severe cardiac, cleft lip, cleft palate, and other cardiac malformations compared to β-lactams.

Notably, the risk of malformation was not higher with nitrofurantoin compared to β-lactams. The findings were consistent across sensitivity analyses, although fluoroquinolone comparisons should be interpreted with caution due to limited statistical power.

The study’s limitations include its non-randomized design, which may subject the results to residual confounding, possible outcome misclassification, exposure misclassification, selection bias due to the restriction to live births, and non-generalizability of the results to uninsured or Medicaid-insured populations.

Overall, the results support current recommendations for caution in using TMP-SMX in the first trimester but do not support limiting nitrofurantoin use.

Cardiovascular disease (CVD) risk prediction models have improved the ability to stratify adults across the CVD risk spectrum. Researchers at Sutter Health and colleagues at Stanford University tested the performance of the American Heart Association’s Predicting Risk of CVD Events (PREVENT) equations in the six largest Asian subgroups as well as in Mexican and Puerto Rican Hispanic subgroups.

The findings, published June 25 in JAMA Cardiology, showed the PREVENT equations accurately predicted CVD, atherosclerotic CVD (ASCVD) and heart failure events across broad, self-identified Asian and Hispanic patient populations.

The burden of heart disease, one of the biggest health problems in the U.S., is likely to grow as the population gets older. Making sure risk tools work for all our patients is key to giving the best care possible.

Advancing cardiovascular health for all

“We led this study to uncover findings that may inform better cardiovascular healthcare for all. In the original validation, PREVENT equations demonstrated good discernment and calibration among racial and ethnic groups, but the model performance among Asian and Hispanic subgroups had not been previously described,” said Xiaowei (Sherry) Yan, Ph.D., senior scientist at Sutter Health’s Center for Health Systems Research and first author of the study. “Our findings showed the PREVENT models performed well across multiple subgroups, with modest variation across individual Asian and Hispanic populations.”

Study overview

Dr. Yan and colleagues conducted an electronic health record–based retrospective cohort study of 361,778 primary care patients aged 30 to 79 years across Sutter Health – a large integrated health system in Northern California caring for more than 3.5 million patients across urban, suburban and rural communities – from January 2010 to September 2023. Patients who had at least two primary care visits during the study period were eligible for the study. Among patients who met the inclusion criteria, the mean age was 54.6 years; 53% were female; 22% were non-Hispanic Asian and 11% were Hispanic.

Key findings

Results showed the PREVENT equations appropriately predicted risk in contemporary diverse Asian and Hispanic subgroups with modest variation in performance across the subgroups studied.

• Over a mean follow-up of 8.1 years, there were 22,648 (6.3%) CVD events among study subjects.
• The predictive accuracy, as demonstrated through use of statistical measures such as the C-statistic and calibration slope, was high for the outcome of total CVD among the Asian and Hispanic populations.
• When examined among the subgroups studied, predictive accuracy for total CVD remained high.
• There were small differences in the performance of atherosclerotic CVD and heart failure PREVENT equations among racial and ethnic groups and subgroups.

The path forward

The burden of CVD and its risk factors is projected to increase across the U.S. in the coming decades, so the ability to more accurately estimate CVD risk in all the communities we serve is more critical now than ever. Although best practices for clinical implementation of the PREVENT CVD risk prediction models should be further investigated, we believe they are an important step forward for communities that have been historically underrepresented in CVD research.”

Powell Jose, M.D., FACC, Sutter Medical Group cardiologist and section chief of general cardiology for Sutter’s heart and vascular service line

Dr. Yan, Dr. Jose and colleagues shared study limitations: they were unable to fully examine all Asian and Hispanic subgroups. Moreover, comparisons of predictive utility of PREVENT and pooled cohort equations were limited by small sample sizes in the Mexican and Puerto Rican Hispanic subgroups.

To better inform clinical application of the study findings, future work may focus on providing clinically sensible cutoffs based on PREVENT ASCVD risk to guide treatment decisions.

Source:

Journal reference:

Yan, X., et al. (2025). Performance of the American Heart Association’s PREVENT Equations Among Disaggregated Racial and Ethnic Subgroups. JAMA Cardiology. doi.org/10.1001/jamacardio.2025.1865.

A new study led by investigators at the UCLA Health Jonsson Comprehensive Cancer Center may help explain why certain liver tumors return quickly after thermal ablation, a widely used minimally-invasive, image-guided technique that kills cancer cells by applying intense heat through a needle-like probe.

The team found that the sugar-binding protein Galectin-1 (Gal-1) plays a critical role in helping hepatocellular carcinoma, the most common form of primary liver cancer, resist thermal ablation and even thrive after being treated with high heat. 

“We found that Gal-1 fuels cancer cells by boosting their ability to produce energy through sugar metabolism, allowing them to resist the effects of thermal stress,” said Dr. Jason Chiang, assistant professor of Radiological Sciences at the David Geffen School of Medicine at UCLA and senior author of the study. “It facilitates production of the additional energy required for liver cancer cells to continue growing, even after being exposed to thermal ablation. This helps the cells not only bounce back quickly after ablation but progress even faster on follow up imaging.”

The discovery, published in Hepatology, points to a promising new strategy that involves targeting Gal-1 to block the cancer’s survival mechanism. This combined approach could enhance the effectiveness of thermal ablation for people with early-stage, non-resectable liver cancer, and reduce the risk for progression after treatment. 

While ablation typically destroys cancer cells at the center of the treated area and can be curative, up to 40% of patients eventually experience cancer recurrence, often at the tumor’s edge where the heat is less intense.

We’ve long known that the center of the tumor is destroyed by ablation, but the edges often remain vulnerable. What we didn’t fully understand was how some of these peripheral cancer cells managed to resist the peri-ablational heat, but we now know that Gal-1 seems to play a critical role in helping them survive and continue growing.”

Tu Nguyen, medical student at the David Geffen School of Medicine at UCLA, and first author of the paper

To better understand how Gal-1 works and influences liver cancer treatment, researchers analyzed 58 treatment naïve pre-ablation biopsy samples from patients with early-stage liver cancer and subsequently found to have either responded or had local recurrences to the ablation treatment. Using advanced lab techniques to analyze protein profiles of the pre-ablation biopsy samples, they found Gal-1 to be overproduced in tumors that had rapid recurrence after thermal ablation.

Using patient biopsy samples, genetically modified cell cultures and mouse cancer models, the researchers showed that Gal-1 enhances cancer cells’ ability to use sugar through a process called glycolysis, even in the face of thermal stress. They also found Gal-1 helps feed another major energy-producing system in cells, known as the tricarboxylic acid (TCA) cycle. Together, these metabolic pathways provide a survival advantage for tumor cells with higher Gal-1 levels after exposure to sublethal heat found in ablation zone peripheries, allowing them to quickly regrow after ablation.

While Gal-1 has previously been linked to cancer spread and resistance to therapy in other tumor types, this study is among the first to connect liver cancer recurrence to a specific metabolic mechanism driven by Gal-1, the researchers noted.

To test a potential pharmaceutical solution, the team paired thermal ablation with a drug that blocks Gal-1, called OTX008. This is a small-molecule inhibitor that binds selectively to Gal-1 to disrupt its function within tumor cells. When tested in mice, the combined treatment approach led to a 2-fold reduction in tumor size and a significant decrease in cancer cells’ ability to produce energy, compared to either treatment alone. These effects were closely linked to lower levels of the Gal-1 protein in tumors treated with the combination therapy, suggesting that Gal-1 inhibition could sensitize liver tumors to ablation and reduce recurrence risks. 

“By blocking Gal-1, we’re not just making standard-of-care thermal ablation work better in early-stage liver cancer, but we may also be opening doors to better treatment options across all stages of liver cancer,” said Chiang. “Gal-1 is an evolutionarily conserved protein that is utilized in not only cancer metabolism, but also in immunology and cancer signaling pathways. There is thus tremendous potential in disrupting Gal-1 to also improve response rates of current drugs that are normally used to treat advanced stage liver cancers.”

While more studies are needed to confirm the results in human patients, the research shows considerable clinical promise for improving patient outcomes. The discovery not only identifies a key metabolic driver of liver cancer recurrence but also introduces a potential new therapeutic target. By integrating Gal-1 inhibition into existing treatment strategies, clinicians may be able to eliminate residual tumor cells, reduce recurrence rates and potentially extend this benefit to more advanced stages of the disease.

Other authors of this study, all from UCLA, are Yonghwan Shin, Aravinth Ruppa, Abigail Krall, Janet Pham, Po-Chun Chen, Hannah Mirmohammadi, Pedram Keshavaraz, Richard Finn, Vatche Agopian, Samuel French, Heather Christofk, David Lu and Steven Raman.

The work was supported in part by the UCLA Department Exploratory Research Grant, the UCLA Health Jonsson Comprehensive Center Fellowship Grant, and the Radiological Society of North America Research Scholar Grant. 

This new article publication from Acta Pharmaceutica Sinica B, discusses how SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood.

In this study, an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) was identified in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice.

It was demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, alternative splicing events were investigated and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation.

In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, lomitapide was identified as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis.

Collectively, these findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

When we’re taking antibiotics, some of the dose is excreted with urine and feces and ends up in our wastewater. The presence of this low dose of antibiotic creates an opportunity for resistant bacteria to evolve. Scientists studying antibiotic resistant bacteria in wastewater at a treatment plant discovered multi-drug resistant strains of bacteria species which are usually not dangerous to healthy people, but which could transmit genes for antibiotic resistance to much more dangerous bacteria like E. coli. 

The scientists then challenged the bacteria with natural compounds which could potentially be included in wastewater treatment to kill off bacteria and fight antibiotic resistance. The most effective were curcumin, which comes from turmeric, and emodin, from rhubarb. 

“Without improved treatment, wastewater could serve as a breeding ground for ‘superbugs’ that may enter water resources such as rivers, lakes, and reservoirs, posing potential risks to public health,” said Dr. Liyuan ‘Joanna’ Hou of Utah State University, senior author of the article in Frontiers in Microbiology. “Our goal was to isolate and characterize multidrug-resistant bacteria, explore the molecular mechanisms of resistance through whole-genome sequencing, and assess the potential of natural compounds as alternative mitigation strategies.” 

Survival of the resistant 

Antibiotic resistance develops when bacteria evolve to be less vulnerable to antibiotics. This is more likely to happen if bacteria are exposed to a dose of vaccine which is too low to kill them all; the survivors develop resistance. Someone infected with these resistant bacteria may then find that their treatment doesn’t work, potentially making routine surgery or illness much more dangerous. 

Some bacteria are resistant to several antibiotics; these infections are often treated with ‘last resort’ drugs like colistin. However, when Hou and her colleagues tested samples of effluent from a wastewater treatment plant in Logan, Utah, they found some colonies of bacteria that were resistant even to colistin. This underlines the urgency of finding ways of preventing and treating bacterial infection which minimize the use of antibiotics. 

The scientists screened their samples using one antibiotic, sulfamethoxazole, to identify nine different antibiotic-resistant strains. These strains of bacteria were then tested against multiple classes of antibiotic to see how many they resisted. Their genomes were also sequenced, which allowed the scientists to identify not just the bacteria themselves but genes which contribute to their antibiotic resistance. One strain, U2, which had the highest number and variety of antibiotic resistance genes, was resistant to all the antibiotics tested. 

The strains represented species of Microbacterium, Chryseobacterium, Lactococcus lactis, and Psychrobacter, which are rarely dangerous to most people – but that doesn’t mean their presence is nothing to be worried about. 

While not traditionally classified as top-priority clinical pathogens, some are opportunistic pathogens associated with infections such as pneumonia in immunocompromised individuals. These bacteria could also act as environmental reservoirs, transferring resistance genes to other bacteria, including clinically relevant pathogens.” 

Dr. Liyuan ‘Joanna’ Hou of Utah State University

Fighting back 

The scientists challenged colonies of these bacteria with different concentrations of 11 natural compounds: berberine, chlorflavonin, chrysin, curcumin, emodin, hesperidin, naringin, quercetin, resveratrol, rutin, and 2′-hydroxyflavone. They then looked at different measurements of the colonies’ health – cell growth, biofilm formation, and how active the bacteria were. 

“We selected a panel of compounds primarily derived from plants, such as curcumin from turmeric, quercetin from onions and apples, and emodin from rhubarb,” said Hou. “These compounds were chosen based on their reported antimicrobial or anti-biofilm properties in previous studies and their natural abundance, making them promising candidates for exploring new, environmentally friendly approaches to mitigate resistance.” 

They found that emodin and curcumin were best at inhibiting cell growth and biofilm formation, while curcumin and a higher dose of emodin reduced cell activity – although a low dose of emodin increased activity for several strains. However, Gram-negative bacteria like Chryseobacterium were resistant to all the compounds. 

“While natural compounds like curcumin and emodin show promise in inhibiting Gram-positive multidrug-resistant bacteria, further research is needed,” said Hou. “Future work should include testing these compounds in complex wastewater matrices, exploring synergistic effects with existing treatment processes, and assessing long-term impacts on microbial communities and resistance dynamics. Additionally, scaling up from laboratory studies to pilot-scale trials will be critical for evaluating feasibility and environmental safety.” 

UNAIDS report warns HIV progress at risk as U.S. funding cuts take hold

JOHANNESBURG, South Africa — Decades of progress in the fight against HIV/AIDS are in danger of unraveling, the United Nations Aids Agency (UNAIDS) warned Thursday in its annual report, citing sharp funding cuts from major donors.

The report, launched in South Africa by UNAIDS, says those cuts — especially the sudden withdrawal of U.S. funding — are threatening to reverse gains that have saved millions of lives over the past two decades.

“If the world doesn’t plug this hole,” said Winnie Byanyima, executive director of UNAIDS, “we estimate that an additional six million people will be newly infected in the next four years. We could have four million additional AIDS-related deaths.”

The reports warning comes five months after the Trump administration halted most funding for the President’s Emergency Plan for AIDS Relief (PEPFAR) — the largest single contributor to the global HIV/AIDS response. The decision was made with little warning.

“The sudden withdrawal of the single biggest HIV donor is putting this progress at risk,” Byanyima said during a press briefing in Johannesburg.

Since the start of the epidemic, UNAIDS says 26.9 million lives have been saved through treatment efforts — many of them in sub-Saharan Africa, the region most affected by the virus.

Fallout in South Africa and beyond

South Africa, which has the world’s largest population of people living with HIV, has made major strides. Most of those infected now receive life-saving antiretroviral drugs.

But the fallout is already being felt. At the report’s launch, South Africa’s Health Minister Aaron Motsoaledi called the U.S. cuts “a wake-up call” — and warned of the dangers of depending on a single donor.

“This type of relationship where we depend on one country, and when that country is in some type of negative mood, the whole world collapses — yes, it’s scary,” he said.

Scientific setbacks and a call to action

South African researchers have been at the forefront of global HIV breakthroughs as well as COVID-19 studies. But many trials are now being suspended due to lack of funds.

Dr. Helen Rees, head of the Wits Reproductive Health and HIV Institute in Johannesburg, said the implications are global.

“The research being done for HIV and tuberculosis in South Africa has not only had an impact here, but a huge global impact,” she said.

Rees was recently honored by the World Health Organization for her “outstanding contribution to public health,” but her institute is now facing major U.S. funding cuts.

“Not charity” — a shared fight

Trump has said the shift away from U.S. aid reflects a new emphasis on “trade over charity” in Africa. But UNAIDS’ Byanyima says the sudden withdrawal of U.S. support in February has left UNAIDS with nearly 50% less funding — and no time to prepare for the gap.

“This is not charity,” she said. “This is solving a global problem together. As long as it festers in some parts of the world, it will come back to hit everybody else.”

For longtime HIV activist Nombeko Mpongo in Cape Town, the cuts have felt deeply personal.

“I remember for a few days I felt suffocated, I felt like being choked… It was like a volcano came and took everything away. It felt like a death penalty,” she said.

But after the shock, Mpongo says she rallied.

“I realized — no man, nonsense. Let me fight. Let me reach out to the communities,” she said. “We’ve fought this virus before. We’ll do it again, because hope is what is going to carry us through.”

The time it takes to grow new skin for burns victims could be improved thanks to a new method of cell cultivation using algae, developed by University of Queensland researchers.

Dr. Melanie Oey and her team at UQ’s Institute of Molecular Bioscience combined a new type of Queensland algae, Chlorella BDH-1, with mammalian cells to improve the process of growing tissue cells.

Our work shows muscle cells co-cultivated with the algae grow faster, live longer and require fewer expensive additives.

The algae act like tiny life-support systems that can solve multiple problems at once.”

Dr. Melanie Oey, UQ’s Institute of Molecular Bioscience

The research could benefit tissue engineering and regenerative medicine with accelerated growth of 3D tissues and skin grafts.

In cell cultures the researchers reported more than 80 per cent increase in cell growth, up to 3 times the number of usable cells and cell cultures that remained viable for longer.

There was also a 50 per cent reduction in the need to use animal cells.

The method also has the potential to benefit other applications such as growing cultivated meat more affordably.

Australia’s food regulator Food Standards Australia New Zealand recently approved the sale of lab-grown or cell-cultured meat – created by growing or multiplying individual animal cells – but cost remains a barrier.

“The growing population requires more protein, but it’s the most expensive macronutrient, and animal farming is also a climate concern,” Dr Oey said.

“But growing meat in the lab is expensive largely due to the nutrients and oxygen the cells need and the waste they produce.

“Our research could make cultivated meat a sustainable, affordable, ethically acceptable alternative protein source.”

Other applications for the use of Chlorella BDH-1 algae in cell culture include:

• Growing organoids (artificially grown masses of cells that resemble an organ) to use in testing drugs and avoiding the need for animal testing.
• Pharmaceutical manufacturing with companies able to grow and test cells more efficiently, with lower overheads and fewer inputs.

Dr Oey said the Chlorella BDH-1 algae was chosen because it does not consume glucose and doesn’t compete with mammalian cells for food.

It naturally produces oxygen and removes waste, creating a more supportive environment for muscle cells to thrive.

“In the human body blood delivers oxygen and removes waste, but in a lab setting you don’t have that system,” she said.

“By adding algae we’re essentially creating a mini-symbiosis or mutually beneficial interaction where the algae provide oxygen and take away waste, helping the cells grow better.

“It’s a simple idea with broad potential.

“By working with nature – using algae to improve the cellular environment – we’ve created a scalable way to support healthier, longer lasting and more efficient cell cultures.”

The research is published in Biotechnology Journal.

New research reveals that while losing weight can rejuvenate aging fat tissue, stubborn immune cells keep a “memory” of obesity, offering fresh targets for lasting metabolic health.

Study: Selective remodelling of the adipose niche in obesity and weight loss. Image Credit: Andrey_Popov / Shutterstock

In a recent study published in the journal Nature, researchers utilized next-generation assays to investigate the regulatory factors, cell types, and molecular events involved in human adipose tissue (AT) remodeling. Their landmark study provides the most detailed view yet into how fat tissue transforms during obesity and weight loss.

Study findings reveal that obesity induces cellular senescence, inflammation, and structural stress within fat, which are only partially reversed by weight loss. Notably, senescence reversal was selective, occurring in metabolic adipocytes, vascular cells, and precursors where p21-positive senescent cells were nearly eliminated, but largely persistent in immune cells. In combination with the 171,247-cell strong atlas, these findings provide a revolutionary understanding of fat tissue plasticity, representing the first step towards novel therapeutic directions that may finally overcome obesity’s notorious capacity to bounce back.

Background

Obesity is a metabolic condition characterized by excessive systemic fat accumulation, with potentially lethal outcomes. Clinically defined as a body mass index (BMI) > 30 kg/m², obesity has been linked to several chronic diseases, including type 2 diabetes (T2D), cardiovascular diseases (CVDs), and even certain cancers.

Alarmingly, more than 1 billion humans live with obesity, with today’s suboptimal lifestyle expected to exacerbate this already grim situation. While pharmacological, behavioral, and surgical interventions have demonstrated promise in achieving weight loss, these benefits are often temporary.

These facts reveal our surface understanding of the association and correlation between weight loss and improved obesity-associated health outcomes, while emphasizing our lack of knowledge of the mechanistic interplay governing fat (adipose tissue [AT]) remodeling.

About the Study

The present study aims to address this knowledge gap and progress our war on obesity by deciphering the cellular, molecular, and spatial changes that occur in human AT during obesity and after weight loss.

Study samples (subcutaneous abdominal AT) were obtained from morbidly obese patients (BMI > 35 kg/m²; n = 25; age = 20–70 yrs) and healthy controls (BMI < 26 kg/m²) intra-operatively via laparoscopic bariatric surgery. Follow-up samples were collected five months later for comparative assays. All samples were subjected to single-nucleus RNA sequencing (snRNA-seq) using the Illumina NextSeq2000 platform.

In brief, the study profiled ~100,000 nuclei from fresh biopsies and integrated the resultant sequences with 50,000 additional nuclei from the largest human fat tissue atlas to date. To supplement this single-cell data atlas, the 10x Genomics’ Xenium platform was leveraged to conduct spatial transcriptomics on over 25,000 cells from equivalent cohorts, allowing researchers to observe differences in tissue-specific cell states.

Simultaneously, formalin-fixed paraffin-embedded (FFPE) AT samples were subjected to 5 μm sectioning, 4′,6-diamidino-2-phenylindole (DAPI) staining, and in situ hybridization assays, allowing researchers to both carry out nuclear identification and measure gene activity directly within intact tissue architecture.

Finally, the study used pathway enrichment (MSigDB), differential expression, transcription factor inference, and spatial niche modeling assays to elucidate the movement, activity patterns, and remodellings of metabolic, immune, vascular, and progenitor cell populations.

Study Findings

The present study makes five key findings:

1. Weight loss selectively reverses senescence in metabolic, vascular, and precursor cells

   Metabolic adipocytes, precursor cells, and vascular cells of patients with obesity were found to express senescence-associated secretory phenotype (SASP) genes and other markers of cellular senescence. These cells contribute to fibrosis, immune signaling, and local tissue stress.

   Notably, following weight loss (bariatric surgery), the fraction of “stressed” adipocytes (AD3) was observed to decrease dramatically (from 55% to 14%; P < 0.0001), and p21-positive senescent cells were nearly eliminated in these lineages. However, senescence persisted in immune cells (macrophages), suggesting only partial and cell-type-specific rejuvenation of the adipose niche.

2. Immune cells retain inflammatory programming post-weight loss

   While the infiltration of lipid-associated macrophages (LAMs) was observed to decrease following weight loss, these LAMs retained inflammatory signature (TREM1 and TLR2) expression, indicating transcriptional memory that may predispose to metabolic dysfunction and potentially explain obesity’s frequent reappearance.

3. Adipocyte metabolism globally activates during weight loss but fails to restore lean-state flexibility

   Weight loss enhanced substrate cycling (e.g., triglyceride hydrolysis/resynthesis) and branched-chain amino acid breakdown, but metabolic parameters (e.g., insulin sensitivity) remained suboptimal relative to lean baselines.

4. Weight loss reduces structural tissue stress and fibrosis

   Weight loss was observed to substantially downregulate the expression of genes (e.g., LOX, ACTA2, and VGLL3) involved in fibrosis and cytoskeletal tension, resulting in reduced adipocyte stiffness and inflammation.

5. Spatial mapping reveals stress niches adjacent to immune hotspots

   The study identified five functional tissue niches: adipocyte, vascular, stress, arterial, and stem-like zones. Stressed cells formed distinct “stress niches” adjacent to immune-enriched arterial zones, indicating microenvironments of obesity-caused damage with delayed recovery. Several stress-associated factors (THBS1, NAMPT, AREG) were found to be enriched in obesity and reversed by weight loss (P < 0.05), highlighting them as potential therapeutic targets.

a, Graphical representation of the primary study cohort (left; single-nucleus analyses in n = 25 obese (OB) people before and after WL and n = 24 lean (LN) people, with spatial analyses in n = 4 people per group) and AT anatomical location (right). b, Clinical characteristics of the primary cohort (n = 24 LN and 25 paired OB–WL donors). Boxplot, median interquartile range minimum and maximum. BMI, body mass index (kg m^–2); F insulin, fasting insulin (mIU L^–1); HbA1c, haemoglobin A1c (%); HDL, high-density lipoprotein cholesterol (mM); DBP, diastolic blood pressure (mm Hg). c, Uniform manifold approximation and projection (UMAP) of 145,452 human AT cells (n = 74 samples of the primary cohort and n = 13 samples of the Emont published cohort¹¹, single nucleus). ASC, adipocyte stem cells; APC, adipocyte progenitor cells; Mono, monocytes; DCs, dendritic cells; ILCs, innate lymphoid cells. d, Cell-type proportions (for the cell types in c) in the combined cohort, mean per group, and for each sample (single nucleus). e, Correlations between cell types and clinical traits (Pearson, LN and OB samples only, single nucleus). Illustration in a created using BioRender (Scott, W., https://BioRender.com/rtmnzaj; 2025).

Conclusions

This study marks a prominent leap in scientific understanding of adipose tissue biology, highlighting that while weight loss can partially and selectively reverse the cellular damage inflicted by obesity (reducing inflammation, senescence in specific lineages, and tissue stress), some immune and metabolic programs retain obesity-associated signatures, potentially explaining the stubborn tendency for weight to return.

The findings highlight fat as a complex, adaptive organ exhibiting cell-type-specific memory, suggesting that future interventions targeting unresolved senescence (e.g., in macrophages) or niche-specific stress signals (e.g., THBS1/NAMPT) may improve long-term outcomes.

More than 75% of children and teenagers experience depression or anxiety, prompting parents to seek effective ways to support their mental health. New research from the University of South Australia suggests that regular exercise may offer a powerful solution.

The study, described as the largest meta-meta-analysis of its kind, examined 375 clinical trials involving more than 38,000 young people. Researchers found that when children participated in structured exercise programs, their symptoms of depression and anxiety improved significantly.

Different exercises target different conditions

The research revealed that specific types of exercise work better for different mental health conditions. Anxiety symptoms improved most through low-intensity, resistance exercises, such as light weights or gentle circuit activities. Depression symptoms showed the greatest improvement through moderate-intensity, mixed-mode, and resistance training, including circuits that combine aerobic and strength programs.

The study found that programs lasting fewer than three months were particularly effective. The biggest improvements in depression symptoms occurred in programs lasting fewer than 12 weeks, suggesting that benefits can emerge relatively quickly, especially for children aged 12 and over.

Interestingly, researchers found no significant differences among the frequency of exercise sessions per week. Children with depression and ADHD showed the greatest improvements from exercise interventions.

Low-cost alternative to traditional treatments

Lead researcher Dr Ben Singh described the findings as presenting parents with a non-invasive, low-cost solution to combat poor mental health in children.

“Depression and anxiety are among the most prevalent mental health issues affecting children and teenagers worldwide,” Singh said. “Evidence-based treatment guidelines often recommend cognitive behaviour therapy and antidepressants as first-line interventions, yet 40 to 60 percent of children don’t receive treatment or fail to gain sufficient benefits, so we clearly need alternatives.”

Singh emphasised that exercise represents a widely accessible strategy that could make a real difference to children’s mental health. He noted that while people generally understand exercise is good for health and wellbeing, little evidence previously showed how exercise works for kids or which types might be more effective than others.

Exercise as core mental health care

Senior researcher Prof Carol Maher highlighted the importance of incorporating exercise into mental health care for children and teenagers.

“Exercise should be a core part of mental health care for children and teens, whether at school, in the community, or clinical settings,” Maher said. “Short, structured programs that include strength training or a mix of activities seem especially promising, but simply exercising, even for short amounts of time will deliver benefits.”

Maher reassured parents that expensive gym memberships or training programs are not necessary. Play-based activities, games, and sport all represent valuable forms of movement that can support mental wellbeing.

“The key message is simple: get active and keep active,” Maher said. “Even short bursts of movement can make a real difference to a child’s mental health and wellbeing – especially for those who are struggling.”

The research demonstrates that exercise offers an effective, accessible lifestyle intervention that can immediately improve mental health issues in children without first defaulting to medicines.

Discover how a small addition of cricket flour can turn everyday pasta into a powerhouse of nutrition, combining eco-friendly protein, minerals, and prebiotic fiber, all without compromising safety or taste.

Study: Cricket Flour for a Sustainable Pasta: Increasing the Nutritional Profile with a Safe Supplement. Image Credit: Giedrius Akelis / Shutterstock

A recent study in the journal Foods evaluates the nutritional profile of cricket flour and its potential as a sustainable food source.

Perception and reality of Insect-based foods

Insects are rich in high-quality proteins, beneficial fatty acids, vitamins, fiber, and essential minerals (e.g., zinc, iron, and selenium), making them a favorable nutrient source that could be exploited to fight malnutrition. Besides a high nutritional profile, insect farming has a lower risk of zoonotic disease transmission, emits fewer greenhouse gases, and requires significantly less water and space, compared to traditional livestock farming.

In many parts of the world, including Asia, Africa, and Latin America, insects have been traditionally consumed as food. Insect-based products are highly regulated under European legislation and require prior authorization before commercialization. Although numerous studies have documented the multiple benefits of insect-based food products, they still face cultural resistance, primarily due to unfamiliarity and a fear of novelty, or neophobia.

A previous study has highlighted the nutritional benefits and safety profiles of cricket (Acheta domesticus) flour. This study has shown that the addition of cricket flour to baked goods enhances the flavor and aroma of the product, thereby improving consumer acceptance.

Scientists believe that incorporating insect-based ingredients into traditional foods could enable the gradual integration of these products into the Western diet. The paper emphasizes that strategies such as blending cricket flour into familiar foods and providing clear information about its nutritional value are important for consumer acceptance in Western markets.

About the study

The current study investigates the key nutrient components of cricket flour and a commercially available mixture of durum wheat and cricket flour (containing 10% w/w Acheta domesticus flour). Wheat flour was used as a reference, and wheat pasta served as a control (CTR). An expert chef prepared fettuccine-shaped pasta.

Protein, fatty acid, and mineral contents, such as iron (Fe), copper (Cu), zinc (Zn), sodium (Na), potassium (K), calcium (Ca), and magnesium (Mg), were analyzed using a standard procedure.

The researchers also analyzed chitin content (a fiber with potential prebiotic benefits), total petroleum hydrocarbons (TPH), and polycyclic aromatic hydrocarbons (PAHs) to assess safety.

Study findings

Gravimetric analysis indicated that the ash content in cricket flour constituted 4.2% of the dry sample weight. The moisture content of CTR and wheat–cricket pasta, after 48 hours of drying, was 14.04% and 11.07%, respectively.

The water activity (Aw) values for the control pasta and wheat–cricket pasta were 0.83 and 0.64, respectively. These Aw values for the flours were similar to those measured in dried pasta and other cereal-based products. The Aw values, falling within the recommended range of <0.6 for dry raw materials, indicate high stability, structural integrity, and functionality of the flours during storage. A low water activity also ensures consistent behavior during processing and formulation.

In line with previous findings, the current study indicated an Fe content of 10.8 mg/100 g in cricket flour, which is higher than the Fe content of other common insect-based novel foods containing Tenebrio molitor and Ruspolia differens. In comparison to wheat flour, the Fe content in cricket flour is nearly ten times higher. A similar trend was also observed for Zn (22 mg/100 gram in cricket flour, compared to 0.84 mg/100 gram in wheat flour) and Cu (3.4 mg/100 gram in cricket flour, compared to 1.6 mg/100 gram in wheat flour).

High K (886 mg/100 g), Na (389 mg/100 g), and Ca (973 mg/kg) concentrations were measured in cricket flour. In contrast, wheat flour contained only 133 mg/100 g of K, 20 mg/kg of Na, and 200 mg/kg of Ca. However, the authors note that while cricket flour is rich in several key minerals, consuming enough to meet the full daily intake for nutrients such as calcium, magnesium, or potassium would require unrealistically high amounts; in practical terms, cricket flour is best used to complement other dietary sources.

According to the total fat content, cricket flour contained 11% total fat, and pasta prepared using a mixture of wheat and cricket flour contained approximately 2%. The fat content in insects typically varies among species and even within the same species due to physiological adaptations associated with diet, environmental conditions, and temperature.

Upon consuming 100 grams of cricket flour, 23% of the energy was found to be derived from metabolizing fats. Saturated fatty acids (SFA) accounted for 42% of the total fatty acids, polyunsaturated fatty acids (PUFA) for 41%, and monounsaturated fatty acids (MUFA) for 17%. Previous studies have shown that a diet rich in SFAs leads to an increase in serum low-density lipoprotein levels, thereby increasing the risk of coronary heart disease.

Percentages of fats in different flours investigated.

In cricket flour, short-chain SFAs were found to be absent, implying that they do not increase blood cholesterol levels. Palmitic and myristic acids were detected in the cricket flour samples. The current study indicated that consumption of cricket flour contributes to 9.8% of total energy from saturated fats, while pasta with wheat-cricket flour provides 1.9% of total energy from SFAs.

Cricket flour contained 17% oleic acid, a nutritionally significant MUFA, and these levels are comparable to traditional wheat pasta (15%) and pasta prepared with wheat-cricket flour. Previous studies have demonstrated that oleic acid reduces low-density lipoprotein (LDL) cholesterol, which has protective effects against cardiovascular diseases, neurodegenerative disorders, and certain types of cancer.

Linoleic acid, a polyunsaturated fatty acid, was found at a high concentration in cricket flour, accounting for 39% of the total fatty acids. An increased intake of linoleic acid has been associated with a reduced risk of coronary heart disease.

While cricket flour is considered healthy (Health Promoting Index >1), it has relatively higher atherogenicity (AI) and thrombogenicity (TI) indices compared to wheat flour. These indices, which reflect potential cardiovascular risk, are improved when cricket flour is blended with wheat flour, as in the mixed pasta.

The current study estimated the total amino acid content in cricket flour to be 60%, which was significantly higher than that of most commonly consumed foods. Both cricket flour and mixed flour samples showed higher levels of nearly all measured amino acids, including alanine, valine, and lysine, compared to wheat-based ones. However, compared to mixed flour, pure cricket samples had a higher concentration of amino acids.

Importantly, the study showed that a 100 g serving of cricket flour can provide 100% of the recommended daily intake for essential amino acids, a level that surpasses most conventional food sources.

The protein content of cricket flour is notably higher than that of many conventional foods, including meat, cheese, and wheat flour. The study also notes that chitin, a component of cricket flour, may act as a prebiotic fiber, supporting gut health. Recent research supports chitin’s role as a prebiotic that could benefit human digestive health.

A higher concentration of total petroleum hydrocarbon (TPH) was estimated in cricket flour samples than in other flour and pasta samples. All samples indicated a Carbon Preference Index (CPI) above 1, indicating a biogenic origin of the hydrocarbons. The study also identified that the polycyclic aromatic hydrocarbons (PAHs) found in cricket flour were primarily of pyrogenic (combustion) origin, not petrogenic (industrial), based on diagnostic ratios. Additionally, polycyclic aromatic hydrocarbon (PAH) levels in cricket flour were low and well below established safety thresholds for food products. The study concludes that both TPH and PAH concentrations in cricket flour do not pose significant health risks and confirms its suitability for human consumption.

Conclusions

In comparison to commercially available wheat flour, the cricket flour contained a higher concentration of protein and essential minerals, such as Na, Ca, Fe, and K. Notably, addition of 10% of cricket flour to wheat flour to make pasta substantially improves the nutritional profile and reduces the amount required to meet recommended daily intakes for several key nutrients. However, for some (such as calcium or magnesium), additional dietary sources would still be needed.

The authors highlight that, while cricket flour shows strong potential as a sustainable, nutrient-rich food supplement, its integration into traditional foods such as pasta—at modest levels—offers a feasible way to enhance nutrient intake without overwhelming sensory or cultural barriers. Consumer acceptance and gradual introduction, supported by clear communication of nutritional benefits, will be key to wider adoption.