👤 Mohd Farhan

Neuroplasticity, the brain's capacity to adapt and reorganize in response to experiences and environmental changes, is fundamental to cognitive aging. As individuals age, cognitive functions such as memory, processing speed, and executive function commonly decline, driven largely by changes in neuroplasticity mechanisms like synaptic plasticity, neurogenesis, and functional reorganization. Synaptic plasticity is a well-established mechanism supporting learning and memory across the lifespan, whereas adult neurogenesis, robustly demonstrated in rodents, remains highly limited and controversial in the adult and aged human brain, with evidence largely restricted to rare post-mortem observations and injury-associated conditions. Functional reorganization allows the brain to adapt to structural changes, helping to preserve cognitive function despite age-related decline. Several factors, including oxidative stress, neuroinflammation, and hormonal shifts, exacerbate the decline in neuroplasticity, accelerating cognitive deterioration. Various interventions, including cognitive training, physical exercise, and pharmacological approaches, have demonstrated the potential to promote neuroplasticity and support cognitive health in aging populations. However, one of the major challenges is tailoring these interventions to the unique needs of individuals, as well as identifying novel therapeutic targets for intervention. To effectively address the cognitive decline associated with aging, future research should focus on developing personalized strategies and innovative techniques to enhance or modulate specific neuroplasticity-related processes under defined conditions in the aging brain. These advancements may provide better tools for delaying, mitigating, or even reversing age-related cognitive decline, improving quality of life for older individuals. Show less

Dyslipidemia remains a central contributor to residual cardiovascular risk despite the widespread use of statins. Obicetrapib, a selective cholesteryl ester transfer protein (CETP) inhibitor, has shown potential as an adjunctive lipid-lowering therapy by favorably modifying key lipid parameters. This study aimed to systematically evaluate the lipid-lowering efficacy of obicetrapib based on current evidence from randomized controlled trials (RCTs). A comprehensive literature search was conducted on PubMed, Embase, Scopus, and ClinicalTrials.gov to identify RCTs assessing the lipid-lowering effects of obicetrapib. Mean differences (MDs) with 95% CIs were calculated using a random-effects model. Nine RCTs (n = 3706) were included. Patients treated with obicetrapib exhibited significant reductions in low-density lipoprotein cholesterol (LDL-C) (MD: -36.5% [95% CI: -41.1 to -31.9]), apolipoprotein B (Apo-B) (MD: -23.8% [95% CI: -28.2 to -19.3]), non-high-density lipoprotein cholesterol (non-HDL-C) (MD: -30.9% [95% CI: -34.6 to -27.1]), and lipoprotein (a) [Lp(a)] (MD: -36.1% [95% CI: -44.4 to -27.8]) compared to placebo. High-density lipoprotein cholesterol (HDL-C) levels significantly increased (MD: 142.6% [95% CI: 128.6-156.6]). Triglyceride levels did not differ significantly (MD: 0.13% [95% CI: -7.01 to 7.26]). Moreover, combination therapy with ezetimibe led to greater reductions in LDL-C by 17.8% (95% CI: 12.05-23.6), Apo-B by 9.7% (95% CI: 5.8-13.7), and non-HDL-C by 17.5% (95% CI: 12.3-22.8), compared to monotherapy. Obicetrapib significantly improves key lipid parameters, including LDL-C, Apo-B, non-HDL-C, HDL-C, and Lp(a), with enhanced efficacy in lowering LDL-C, Apo-B, and non-HDL-C when combined with ezetimibe. These findings support its potential role in comprehensive lipid management strategies. Show less

Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder characterized by bone fragility and reduced bone mass generally caused by defects in type I collagen structure or defects in proteins interacting with collagen processing. We identified a homozygous missense mutation in SEC16B in a child with vertebral fractures, leg bowing, short stature, muscular hypotonia, and bone densitometric and histomorphometric features in keeping with OI with distinct ultrastructural features. In line with the putative function of SEC16B as a regulator of trafficking between the ER and the Golgi complex, we showed that patient fibroblasts accumulated type I procollagen in the ER and exhibited a general trafficking defect at the level of the ER. Consequently, patient fibroblasts exhibited ER stress, enhanced autophagosome formation, and higher levels of apoptosis. Transfection of wild-type SEC16B into patient cells rescued the collagen trafficking. Mechanistically, we show that the defect is a consequence of reduced SEC16B expression, rather than due to alterations in protein function. These data suggest SEC16B as a recessive candidate gene for OI. Show less

Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of Show less