👤 Urwa Tariq

Global studies have shown a bidirectional association of gestational diabetes mellitus (GDM) with postpartum depression (PPD). Despite high GDM prevalence in Pakistan (3.3%-17.8%), no prior studies have explored its link with PPD. In this study, association between GDM and risk of developing PPD was investigated and risk factors for PPD were identified using the gold-standard Edinburgh Postnatal Depression Scale (EPDS). Evidence suggests that PPD has strong genetic basis. The BDNF gene is a known candidate for PPD pathogenesis, while the orexin system is linked to arousal, energy metabolism, with emerging role in neuropsychiatric disorders. This study is the first study to explore association of orexin SNP ORX1 10914456 with PPD together with the BDNF SNP rs6265 (Val/Met66), among participants with and without GDM diagnosis. Among 1,000 women approached in hospitals of Islamabad, Rawalpindi, 800 met inclusion criteria (400 GDM, 400 non-GDM controls) and were genotyped for BDNF and orexin SNPs. Participants completed the EPDS 1 week postpartum. Using a cutoff of ≥13, 84.9% of GDM patients and 18% of non-GDM controls scored ≥13 on EPDS (χ2 = 78.337, p < 0.00001). Multivariate logistic regression revealed GDM diagnosis, BMI >25, fasting plasma glucose >126 mg/dL, 31-39-week gestation, <12 years of education, and urban locality as significant risk factors for PPD. GDM diagnosis increased odds of PPD by 2.5-fold (OR = 2.5, 95% CI: 21.48-4.31, p < 0.0001). The orexin SNP Orx1 10914456, CC genotype and BDNF SNP rs6265, AA genotype increased the odds of having higher EPDS scores in GDM patients by 3.11 (OR = 3.11, 95% CI: 1.29-7.47, p < 0.001) and 3.3 (OR = 3.3, 95% CI: 1.31-8.13, p = 0.04, p < 0.05), respectively, in comparison to other genotypic variants. Our study supports orexin and BDNF system-targeted therapies for PPD. Show less

Globally, Alzheimer's disease (AD) is the leading cause of dementia. Key symptoms include extracellular amyloid β (Aβ) accumulation, tau hyperphosphorylation, synaptic dysfunction, neuroinflammation, and BBB disruption. Integrative solutions are needed because conventional medicines merely relieve symptoms and cannot stop disease progression. Low-density lipoprotein receptor-related protein 1 (LRP1) plays a crucial role in Aβ efflux, tau control, neuroinflammatory signaling, and neurovascular unit maintenance, making it a promising but unexplored therapeutic target. In AD and aging, LRP1 deficiency worsens clearance, vascular impairment, and neurodegeneration. Ligand-functionalized nanocarriers, antibodies, and gene manipulation show preclinical promise, but lower receptor expression, systemic off-target effects, and BBB penetration are challenges. Recent advances suggest innovative strategies, such as upregulating hepatic LRP1 for peripheral Aβ storage, modulating cofactors like ANKS1A (ankyrin repeat and SAM domain containing protein 1A) for receptor trafficking, using engineered nanoparticles or extracellular vesicles as Aβ decoys, preventing negative apolipoprotein E: ApoE4 and LRP1 interactions, and promoting neuroprotective pathways through LRP1 modulation. Endothelial-targeted gene therapy and dual transport rebalancing, which increases LRP1-mediated efflux and decreases RAGE-driven influx, are complementary. These precision strategies reposition LRP1 as a multifaceted therapeutic gateway rather than a clearance receptor, combining biomarker-driven patient stratification with next-generation delivery systems to transform AD disease-modifying therapies. Show less

Memory-like responses in innate immune cells confer nonspecific protection against secondary exposures. A number of microbial agents have been found to induce enhanced or diminished recall responses in innate cells, however, studies investigating the ability of probiotic bacteria to trigger such effects are lacking. Here, we show that priming of human monocytes with a secretome from the gut probiotic bacterium Show less