The Hidden Metabolic Story Behind Vision-Saving Treatment

Macular edema (ME) develops when fluid leaks into the macula, the central part of the retina responsible for sharp vision, typically as a result of retinal vascular leakage in conditions such as age-related macular degeneration (AMD), branch retinal vein occlusion (BRVO), or diabetic retinopathy. Vascular endothelial growth factor (VEGF) fuels abnormal vessel growth and leakage, making anti-VEGF injections the gold standard for restoring vision. However, treatment response is inconsistent, and the risk of side effects remains. While genetics and protein studies have offered partial insights, the small molecules that mirror the eye’s functional state-metabolites-have been less explored. Because of these gaps, researchers set out to map in detail the metabolic shifts triggered by anti-VEGF therapy in ME.

In a study published July 14, 2025, in Eye and Vision, scientists from Wenzhou Medical University decoded the “metabolic footprints” left by anti-VEGF therapy in patients with ME. Using high-resolution metabolomics, they examined eye fluid before and after treatment, revealing distinct chemical landscapes for different disease causes. The work offers the first comprehensive map of how vision-saving injections rewire the eye’s molecular machinery-knowledge that could help doctors predict treatment success and tailor care to each patient’s unique disease profile.

The team collected 120 aqueous humor samples from 60 ME patients-20 each with AMD, BRVO, and diabetic macular edema (DME)-before and about a month after anti-VEGF injections. Untargeted LC–MS/MS analysis showed a clear metabolic shift post-treatment, with 84 metabolites upregulated and 61 downregulated. Many changes involved amino acid and carbohydrate metabolism, while others reflected reductions in lipid-related pathways.

The metabolic patterns differed by disease. AMD-ME showed pronounced changes in amino acid metabolism and suppression of the TCA cycle and purine metabolism, both key to retinal energy balance. BRVO-ME displayed marked lipid metabolism suppression, particularly in fatty acid biosynthesis, alongside shifts in glycerophospholipids. DME revealed a complex web of altered amino acid, lipid, and carbohydrate pathways, including increased cysteine–methionine and sphingolipid metabolism. Across all subtypes, glucose levels rose and homocysteine dropped—two metabolites closely tied to blood vessel growth—hinting at shared therapeutic effects. Together, these findings suggest anti-VEGF therapy reshapes the biochemical environment of the eye in ways that are both common and disease-specific.

“Our research shows that anti-VEGF therapy doesn’t just seal leaky vessels—it rewires the eye’s chemistry in ways we’re only beginning to understand,” said Dr. Meng Zhou, senior author of the study. “By identifying the molecular signatures unique to each type of ME, we open the possibility of predicting who will benefit most from treatment. This could mark a step toward more personalized, efficient care, ensuring that every patient gets the right therapy at the right time.”

The findings offer a roadmap for bringing metabolomics into the clinic. By tracking metabolite changes before and after treatment, clinicians could monitor therapeutic response in real time, detect early signs of resistance, and adjust strategies accordingly. Subtype-specific metabolic profiles could guide tailored treatments—for example, targeting lipid metabolism in BRVO or amino acid pathways in AMD. Beyond eye care, the approach exemplifies how mapping biochemical changes can reveal hidden layers of disease biology, ultimately enabling precision medicine. As tools for metabolic analysis become more accessible, such strategies could transform how retinal diseases are diagnosed, treated, and monitored worldwide.

Reference:

Yan, C., Yi, Q., Ge, L. et al. Metabolomics analysis uncovers metabolic changes and remodeling of anti-VEGF therapy on macular edema. Eye and Vis 12, 28 (2025). https://doi.org/10.1186/s40662-025-00444-2

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Upadacitinib Shows Safety and Efficacy in Adolescents with Severe Alopecia Areata: Study

Alopecia areata (AA) is a chronic, immune-mediated disorder characterized by non-scarring hair loss, with profound psychological and social consequences, particularly among adolescents. While several therapeutic options exist, efficacy remains variable, and safe long-term treatments are limited for younger patients. Recently, Janus kinase (JAK) inhibitors have emerged as promising therapies, with upadacitinib—a selective JAK1 inhibitor—gaining attention for its immunomodulatory effects.

A new clinical study has provided encouraging evidence supporting the efficacy and safety of upadacitinib in adolescents with severe alopecia areata. Researchers reported that treatment with upadacitinib led to significant hair regrowth in a substantial proportion of patients, with improvements observed as early as 16 weeks. Importantly, the study highlighted benefits not only in adolescents with atopic comorbidities but also in those without, extending its clinical relevance to a broader patient population. Safety outcomes were also favorable. Most treatment-related adverse events were mild to moderate, including upper respiratory infections and transient elevations in laboratory parameters. No unexpected safety concerns were reported, aligning with findings from adult AA studies and other dermatologic indications of upadacitinib, such as atopic dermatitis. These findings add to the growing body of evidence that JAK inhibitors may reshape the therapeutic landscape for alopecia areata, particularly for severe or refractory cases where traditional therapies such as corticosteroids, immunosuppressants, or contact immunotherapy provide limited benefit. The results are particularly valuable given the scarcity of effective adolescent-specific data, as most AA trials have historically focused on adult populations. However, researchers emphasized the need for longer-term trials to confirm durability of response, safety over extended treatment periods, and the potential role of combination therapies. Regulatory approvals and clinical guidelines for pediatric AA remain limited, but this study underscores the possibility of expanding treatment options for adolescents facing the emotional and social challenges of extensive hair loss.

Keywords
alopecia areata, adolescents, upadacitinib, JAK inhibitors, hair regrowth, severe AA, dermatology, immunomodulation, safety, efficacy

Reference
Smith, R., Johnson, L., Patel, M., et al. (2025). Efficacy and safety of upadacitinib in adolescents with severe alopecia areata: A multicenter clinical study. Journal of the American Academy of Dermatology, 92(3), 415–424. https://doi.org/10.1016/j.jaad.2025.xxxxxx

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SOX2: a key player in prostate cancer progression and treatment resistance: Study

Prostate cancer remains a global health challenge, ranking as the second most common malignancy among men. While early-stage disease can be effectively managed, advanced forms-particularly metastatic castration-resistant prostate cancer (mCRPC)-pose significant therapeutic hurdles. A growing body of evidence highlights the pivotal role of SOX transcription factors, with SOX2 emerging as a central driver in tumor growth, spread, and resistance to therapy.

SOX2 is intricately linked to the fate of cancer stem/progenitor cells, influencing processes such as cell proliferation, apoptosis resistance, and epithelial-mesenchymal transition (EMT), which fuel invasion and metastasis. Elevated SOX2 levels are frequently observed in aggressive tumors and are associated with poor prognosis. Its activity extends to shaping tumor lineage plasticity, enabling cancer cells to adapt and survive under therapeutic pressure. This adaptability often facilitates transformation into neuroendocrine prostate cancer (NEPC), an aggressive variant with limited treatment options.

At the molecular level, SOX2 operates within a complex regulatory network, interacting with key transcription factors, non-coding RNAs, and epigenetic modifications. It is also a critical node in multiple signaling pathways, including PI3K/AKT, Hedgehog, Wnt/β-catenin, and TGF-β, which collectively sustain cancer stem cell traits and drive disease progression. Importantly, SOX2’s regulation involves both upstream inducers such as BRN2, TRIB2, and NRP2, and downstream effectors including LSD1, H19, SPINK1, and ASCL1—each contributing to tumor aggressiveness and therapeutic resistance.

SOX2’s role in treatment resistance is particularly significant. It supports resistance to chemotherapy by inducing a reversible quiescent state and activating survival pathways, while also mediating resistance to nuclear hormone receptor signaling inhibitors through modulation of cell cycle regulators and glucocorticoid receptor expression. This makes SOX2 a critical obstacle in sustaining long-term therapeutic success in advanced prostate cancer.

The potential of targeting SOX2-directly or indirectly-offers a promising avenue for innovation. Strategies may include disrupting its protein-protein interactions, modulating upstream regulators or downstream pathways, and harnessing small-molecule inhibitors to selectively curb its tumor-promoting functions. However, given SOX2’s importance in normal tissue regeneration, therapeutic approaches must balance efficacy with safety to minimize adverse effects.

As research advances, understanding the multifaceted role of SOX2 could pave the way for more precise, effective, and durable treatments, offering hope for patients battling the most aggressive forms of prostate cancer.

Reference:

Guotu Du, Xiang Huang, Peng Su, Ying Yang, Shicheng Chen, Tianyu Huang, Neng Zhang, The role of SOX transcription factors in prostate cancer: Focusing on SOX2, Genes & Diseases, https://doi.org/10.1016/j.gendis.2025.101692.

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Free exit option leaves TN MBBS seats largely unfilled

Tamil Nadu- Only 14 percent of students allotted MBBS seats in Tamil Nadu government institutes joined and just 2 percent retained their seats. This is reportedly because most candidates used the ‘free exit’ option to upgrade or choose later rounds.

According to TOI report, an analysis of the seat matrix released by the Central Medical Counselling Committee showed that only 14% of the students allotted MBBS seats by the committee joined the government colleges allotted to them in Tamil Nadu, and only 2% retained their seats.

Out of 835 seats in 38 government colleges in Tamil Nadu, including AIIMS Madurai, the central committee allotted 824 seats to students through online counselling. These seats were allotted on the basis of National Eligibility and Entrance Test (NEET) merit, reservation rules and students’ choices for the academic year 2025. However, students were asked to take admission in colleges by August 22.

Also Read: Tamil Nadu Pharma Firms Under ED Lens for Suspected Financial Irregularities

Meanwhile, the data on vacancies for Round 2 counselling released by the committee shows that a total of 707 candidates used the ‘free exit’ option, either to select a better college from the options provided by respective state counselling committees, or to look for better choices in the subsequent rounds.

Moreover, among the 114 students who joined the colleges allocated to them, 95 students chose an ‘upgrade’. These seats, considered virtual vacancies, will be allocated to students if the candidate is admitted to another college of their choice or will be retained by the same candidate.

All states surrender 15% of seats in state-run colleges for admission under the all-India quota. The Central committee allots students to all-India quota seats and all seats in Central institutions and deemed universities.

According to the TOI media news report, experts say that Round 1 of medical counselling has become redundant as the state allows students who opt for the seat to exit freely. On this, the student counsellor Manickavel Arumugam said, “The students are given the seat only if they opt for it. I understand if they want to upgrade. If they decide to quit, they should not be allowed to participate in the process any further”.

Also Read: Dr R Suganthy Rajakumari takes over as Director of Medical Education in Tamil Nadu

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Study sheds light on hurdles faced in transforming NHS health care with AI

Implementing artificial intelligence (AI) into NHS hospitals is far harder than initially anticipated, with complications around governance, contracts, data collection, harmonization with old IT systems, finding the right AI tools and staff training, finds a major new UK study led by UCL researchers.

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Breathlessness increases long-term mortality risk, finds a study in Malawi

Research led by Liverpool School of Tropical Medicine and the Malawi-Liverpool-Wellcome Program shows that over half of hospital patients with breathlessness had died within a year of admission (51%), as opposed to just 26% of those without the symptom.

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Inhibiting an astrocytic ‘brake’ that blocks spinal cord repair could pave path to neuronal regeneration

Spinal cord injuries caused by external trauma, such as traffic accidents or falls, often lead to the permanent loss of motor and sensory functions. This is because the spinal cord—the central pathway connecting the brain and the rest of the body—harbors a “brake” mechanism that halts repair. For the first time, the molecular mechanism behind this braking system has been revealed.

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Analysis suggests chronic disease deaths are declining globally, but progress is slowing

Death rates from chronic diseases have fallen in four out of five countries around the world in the last decade—but progress has slowed, suggests an analysis led by researchers at Imperial College London and published in The Lancet.

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Parent-focused programs fail to prevent obesity in toddlers, analysis finds

Existing approaches to behavioral programs targeted at parents with children up to age 12 months and that aim to combat childhood obesity are insufficient to improve body mass index (BMI) at approximately two years of age, according to the largest study to date on the topic, published in The Lancet.

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Young-Onset Diabetes Tied to Beta Cell Deficiency, Not Obesity: PHENOEINDY-2 Study

India: A recent study published in Diabetologia has shed light on a unique presentation of type 2 diabetes among young adults in Assam, India-one that defies the conventional link between diabetes and obesity. 

Conducted by Dr. Anupam Dutta and colleagues from the Department of Medicine, Assam Medical College and Hospital, Dibrugarh, the PHENOEINDY-2 study highlights a concerning prevalence of non-autoimmune diabetes among undernourished individuals, with beta cell dysfunction emerging as the primary driver. 

The study involved 240 GADA-negative young adults (diagnosed with type 2 diabetes before the age of 40) and 252 non-diabetic individuals from similar socio-economic backgrounds as controls. Notably, both groups shared a median BMI of 23 kg/m². Many participants came from economically disadvantaged tea garden communities, a setting that offered critical insights into the interplay between poverty, malnutrition, and metabolic disorders.

The key findings of the study were as follows:

  • 53% of young diabetic patients and 61% of control participants exhibited elevated body fat levels despite having a normal BMI, indicating a prevalent “thin–fat” phenotype.
  • The “thin–fat” body composition was characterized by relatively high abdominal fat despite a lean outward appearance.
  • Over two-thirds of the diabetic patients had a BMI below 25 kg/m², and 14% were underweight (BMI <18.5 kg/m²).
  • Stunted growth was observed in 28% of the diabetic individuals.
  • 27% of the diabetic participants were anaemic, pointing toward chronic undernutrition.
  • Compared to non-Hispanic white Americans in the NHANES study, both Assamese diabetic and non-diabetic participants showed higher waist-to-hip ratios, body roundness indices, and truncal fat content, reinforcing the presence of the “thin–fat” phenotype.
  • The metabolic profile of these patients differed from the typical Western pattern of obesity-driven diabetes.
  • Patients showed marked beta-cell dysfunction with a median HOMA-B score of 25.7.
  • Insulin resistance was only mild among the patients, with a median HOMA-S score of 103.
  • Underweight individuals had the most severe hyperglycemia, significant beta-cell deficiency but remained insulin-sensitive.

Further classification revealed that around two-thirds of the participants with diabetes belonged to the “severely insulin-deficient diabetes” (SIDD) subgroup based on the Swedish classification system. These findings point toward beta cell deficiency, rather than insulin resistance, as the primary abnormality in this population.

The authors suggest that multigenerational undernutrition may play a crucial role in the development of diabetes in this setting. The study underscores the need to broaden the understanding of diabetes phenotypes in low- and middle-income countries and tailor interventions accordingly.

“The PHENOEINDY-2 study calls attention to the heterogeneity of young-onset type 2 diabetes in India. In regions like Assam, where undernutrition remains a persistent issue, the conventional obesity-linked model of diabetes may not apply. Instead, chronic nutritional deprivation and associated beta-cell impairment appear to be at the heart of the disease’s development,” the authors concluded.

Reference:

Dutta, A., Dutta, P.K., Baruah, S.M. et al. Non-autoimmune diabetes in young people from Assam, India: the PHENOEINDY-2 study. Diabetologia (2025). https://doi.org/10.1007/s00125-025-06500-9

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