👤 Pooja Singla

Metabolic dysfunction-associated steatotic liver disease (MASLD) primarily results from dysregulated lipid metabolism in hepatocytes. However, the mechanisms governing hepatic lipid metabolism remain incompletely understood. Our preliminary experiments demonstrated elevated expression of R-spondin 2 (RSPO2), a matricellular protein, in steatotic livers. Therefore, we investigated the role of RSPO2 in MASLD and potential underlying mechanisms. Comprehensive RSPO2 expression was significantly increased in steatotic livers of high-fat diet-fed wild-type ( These findings identify RSPO2 as a key suppressor of hepatic steatosis and fibrosis, and highlight its potential as a therapeutic target for MASLD. Given the hepatic/extrahepatic complications associated with MASLD (metabolic dysfunction-associated steatotic liver disease) and its high prevalence, it is crucial to decipher the precise molecular mechanisms regulating its pathogenesis to identify novel druggable targets. In this study, we demonstrate for the first time that hepatocyte RSPO2 plays a protective role against hepatic steatosis, fibrosis, and inflammation. Show less

Atherosclerotic cardiovascular disease (ASCVD) is a leading global cause of death. Although statins are the foundation of lipid-lowering therapy, many high-risk patients fail to achieve low-density lipoprotein cholesterol (LDL-C) targets due to intolerance or insufficient response. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as potent agents that address this residual risk. This review summarizes the clinical efficacy, safety, and mechanistic role of PCSK9 inhibitors in cardiovascular risk reduction. Relevant randomized trials, meta-analyses, and observational studies were analyzed, alongside emerging nonstatin therapies including bempedoic acid, inclisiran, and Angiopietin-like 3 inhibitors. PCSK9 inhibitors, such as alirocumab and evolocumab, have shown LDL-C reductions of up to 62% and significant decreases in major adverse cardiovascular events. Trials like Further cardiovascular outcomes research with PCSK9 inhibition in subjects With elevated risk (FOURIER) and Evaluation of cardiovascular outcomes after an acute coronary syndrome during treatment with alirocumab (ODYSSEY OUTCOMES) reported relative risk reductions of 15-24% in select populations. These agents also reduce lipoprotein(a) (Lp(a)) and stabilize atherosclerotic plaques. Additional therapies like inclisiran and bempedoic acid further expand treatment options, particularly for statin-intolerant patients. PCSK9 inhibitors offer a well-tolerated and effective approach to lowering LDL-C and mitigating cardiovascular risk. Their integration, along with emerging therapies, provides a comprehensive strategy to address residual ASCVD risk and improve patient outcomes. This review highlights the pivotal role of PCSK9 inhibitors in achieving significant LDL-C reduction and improving cardiovascular outcomes, especially in high-risk and statin-intolerant populations. By also targeting Lp(a) and promoting plaque stabilization, these agents address multiple contributors to residual ASCVD risk. Incorporating PCSK9 inhibitors and emerging nonstatin therapies into clinical practice offers a powerful strategy to enhance long-term cardiovascular prevention. Show less

Benign prostatic hyperplasia (BPH) is a commonly occurring disease in aging men. It involves cellular proliferation of stromal and glandular tissues leading to prostate enlargement. Current drug therapies show several adverse effects such as sexual dysfunctions and cardiovascular side effects. Therefore, there is a need to develop more effective medical treatment for BPH. In this regard, we aimed to identify genes which play a critical role in BPH. We have obtained the dataset of differentially expressed genes (DEGs) of BPH from NCBI GEO. DEGs were investigated in the context of their protein-protein interactions (PPI). Hub genes i.e. genes associated with BPH were scrutinized based on the topological parameters of the PPI network. These were analyzed for functional annotations, pathway enrichment analysis and transcriptional regulation. In total, 38 hub genes were identified. Hub genes such as transcription factor activator protein-1 and adiponectin were found to play key roles in cellular proliferation and inflammation. Another gene peroxisome proliferator activated receptor gamma was suggested to cause obesity, a common comorbidity of BPH. Moreover, our results indicated an important role of transforming growth factor-beta (TGF-β) signaling and smooth muscle cell proliferation which may be responsible for prostate overgrowth and associated lower urinary tract symptoms frequently encountered in BPH patients. Zinc finger protein Snai1 was the most prominent transcription factor regulating the expression of hub genes that participate in TGF-β signaling. Overall, our study has revealed significant hub genes that can be employed as drug targets to develop potential therapeutic interventions to treat BPH. Show less

The 2014 American Heart Association/American College of Cardiology (AHA/ACC) clinical guidelines recommend cardiac troponin as a superior biomarker to creatine kinase (CK) and creatine kinase-muscle/brain (CK-MB) for the detection of acute coronary syndrome (ACS), namely myocardial infarction and unstable angina. In April 2018, our Emergency Department (ED) transitioned from using standard troponin to using high-sensitivity troponin T, and adopted a clinical guideline consistent with the AHA/ACC. The guideline recommended high-sensitivity troponin T without CK/CK-MB testing in the majority of clinical situations, limiting CK/CK-MB testing to two specific clinical cases: 1) estimated glomerular filtration rate (eGFR) value <15 mL/min, or 2) recent acute coronary syndrome (ACS) event. Per our ED's policy, a "negative" troponin T was defined as being below the limit of detection (LOD) (i.e., <6 ng/L); such a value obtained at least 3 hours after symptom onset "ruled out" an ACS event and did not require a repeat troponin. The goal of this retrospective study was to determine whether the guideline limiting CK-MB testing missed clinically-significant cardiac outcomes (ACS or new diagnosis of coronary artery disease [CAD]) or was associated with mortality. Pre-implementation data (July 1, 2017 - December 31, 2017) was compared with post-implementation data (July 1, 2018 - December 31, 2018). After guideline introduction, CK/CK-MB ordering decreased by nearly 90%, while troponin ordering increased by nearly 20%, likely due to the introduction in June 2018 of high-sensitivity troponin T, which yielded numerous intermediate/indeterminate-range results that prompted repeat testing. Fewer than 1.5% of patients with a "negative" troponin (below the LOD) and a "positive" CK-MB (above the upper limit of normal [ULN]) had ACS or new-diagnosis CAD; patients with either diagnosis did not expire during their hospital stay or within 30 days of their index visit. CK-MB Index, which has a higher specificity than CK, only found ACS or new CAD among 0.8% of positive results. Considering both decreased CK/CK-MB and increased troponin ordering, the net annual direct cost savings in cardiac biomarker testing was extrapolated to $12,700. Had our institution not transitioned to higher cost high-sensitivity troponin ($2.054/unit) from standard troponin ($1.65/unit), and had the rate of troponin ordering increased solely proportionate to the rate of ED visit increase (2% year-over-year) rather than increase nearly 20% (likely due to the transition to high-sensitivity troponin), then the total six-month direct costs on troponin testing would have been $14,632 instead of $21,267.12, and annual direct cost savings would have been $18,945.80 instead of $12,700. The new ED clinical guideline did not result in a significant number of missed ACS or new-diagnosis CAD, and was associated with direct cost savings. These savings probably underestimate total savings, as the reduced number of "false-positive" CK-MB results likely prevented additional costs, such as hospitalization, specialty consultation, coronary calcium CT, echocardiogram, cardiac stress test, and coronary artery catheterization. Show less

Many bacteria have the potential to use specific pesticides as a source of carbon, phosphorous, nitrogen and sulphur. Acephate degradation by microbes is considered to be a safe and effective method. The overall aim of the present study was to identify acephate biodegrading microorganisms and to investigate the degradation rates of acephate under the stress of humic acid and most common metal ions Fe(III) and copper Cu(II). Show less