Publications by authors named "Alka Singh"

Background And Objectives: Metastatic castration-sensitive prostate cancer (mCSPC) imposes a significant economic burden and necessitates more cost-effective treatment strategies. The variability among the components of published economic evaluation models leads to methodological inconsistencies, underscoring the need for an optimal framework to minimise unwarranted structural variation. This paper reviews existing economic evaluations, establishes a comprehensive framework and aims to support future economic evaluations and decision-making in mCSPC.

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Background And Purpose: Liver fibrosis, a progressive liver disease arising from viral or metabolic causes, poses a major global health challenge due to its potential progression to cirrhosis and hepatocellular carcinoma. Due to the complex aetiology and epidemiology of liver fibrosis, most therapies fail in the clinic, and very few drugs have been approved by the US FDA.

Approach: This review highlights the pathophysiological features of liver fibrosis, with a focus on novel targets in hepatic stellate cells (HSCs), key players in the fibrogenesis process, to develop successful therapeutic approaches using both pharmacological agents and active targeting strategies.

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Aim: This study explores the unbinding dynamics of alpha-ketoglutarate (AKG) from wild-type and mutant IDH1/IDH2 enzymes through steered molecular dynamics (SMD) simulations, examining how mutations influence binding, stability and enzymatic behaviour.

Background: Isocitrate dehydrogenase (IDH) enzymes are essential for cellular metabolism, catalyzing the conversion of isocitrate to AKG in the tricarboxylic acid cycle. Mutations in IDH1 and IDH2 lead to the aberrant accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), disrupting normal metabolic processes and contributing to tumorigenesis.

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Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, is the most significant cause of cancer-related death globally, with limited treatment options, including surgical resection, liver transplantation, ablation, chemoembolization, immunotherapy, and radiation. , a plant that is rich in chalcones and flavonoids, has demonstrated interesting anticancer properties. This study assesses the pharmacological effects of extract on HepG2 cells in order to investigate its efficacy as a therapeutic intervention for HCC.

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Objectives: Intestinal fatty acid binding protein (IFABP) is a marker of intestinal epithelial injury and has been studied as a surrogate for predicting villous atrophy. The aim of this study was to evaluate the utility of IFABP in the non-invasive diagnosis of celiac disease (CeD) in children.

Methods: Symptomatic children with positive anti-tissue transglutaminase antibody underwent a duodenal biopsy and IFABP measurement.

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Neurological disorders, encompassing neurodegenerative and neuroinflammatory conditions, present significant public health and clinical challenges. Recent research has elucidated the pivotal role of various enzymes in the onset and progression of these disorders. This review explores the therapeutic potential of targeting these enzymes with natural and synthetic molecules.

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Carcinoid tumors (CTs) are slow-growing neuroendocrine neoplasms that may arise in any part of the body. They usually affect the lungs or gut. Primary intradural extramedullary CTs of the central nervous system are rare; few cases have been reported.

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Neurological disorders are defined by a deterioration or disruption of the nervous system's structure and function. These diseases, which include multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, and schizophrenia, are caused by intricate pathological processes that include excitotoxicity, neuroinflammation, oxidative stress, genetic mutations, and compromised neurotrophic signaling. Although current pharmaceutical treatments relieve symptoms, their long-term efficacy is limited due to adverse side effects and weak neuroprotective properties.

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Biofilm-associated amyloid proteins have emerged as significant contributors to the progression of neurodegenerative diseases, representing a complex intersection of microorganisms and human health. The cross-beta sheet structure characteristic of amyloids produced by gut-colonizing bacteria remains intact, crucial for the resilience of biofilms. These amyloids exacerbate neurodegenerative disorders such as Alzheimer's and Parkinson's by cross-seeding human amyloidogenic proteins like amyloid-beta and α-synuclein, accelerating their misfolding and aggregation.

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Intestinal homeostasis is tightly regulated by the reciprocal interaction between the gut epithelium and adjacent mesenchyme. The Hippo pathway is intimately associated with intestinal epithelial homeostasis and regeneration; however, its role in postnatal gut mesenchyme remains poorly defined. Here, we find that removal of the core Hippo kinases Lats1/2 or activation of YAP in adult intestinal smooth muscle layers has largely no effect; however, Hippo-YAP signaling in the niche-forming Gli1+ mesenchymal cells plays intrinsic roles in regulating intestinal homeostasis.

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Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck. Stagnating survival rates in recent decades, despite advances in the treatment paradigms, surveillance technologies, and multidisciplinary care, leave clinicians with a need for better options for screening, risk-stratifying, and monitoring patients. A growing proportion of patients with HPV-associated SCC have improved outcomes but continue to have a heterogenous response to treatment.

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Background: Adenoid cystic carcinoma (ACC) is a rare glandular malignancy, commonly originating in salivary glands of the head and neck. Given its protracted growth, ACC is usually diagnosed in advanced stage. Treatment of ACC is limited to surgery and/or adjuvant radiotherapy, which often fails to prevent disease recurrence, and no FDA-approved targeted therapies are currently available.

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Article Synopsis
  • * The study focused on evaluating the mutation status of IDH-1, ATRX, and p53 in glioma biopsies, finding a notable IDH-1 mutation in 43.9% of cases, which was associated with specific clinical features.
  • * Results showed that IDH-1 mutations were prevalent in lower-grade tumors and linked to lower tumor proliferation rates, while ATRX and p53 mutations were also common and correlated with the astrocytic tumor type.
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  • Renal stones are on the rise globally, and percutaneous nephrolithotomy (PCNL) is a minimally invasive procedure that effectively removes these stones, though some complications can occur.
  • In a study involving 201 patients who underwent PCNL, the overall complication rate was found to be 21.9%, with most categorized as minor, while 5.5% experienced major complications, but no postoperative deaths were recorded.
  • Factors influencing higher complication rates included being female, larger stone size, hydronephrosis, recent UTI treatment, prolonged surgery duration, and complex kidney stones.
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Brain-derived neurotrophic factor (BDNF) and its downstream tropomyosin receptor kinase B (TrkB) signaling pathway play pivotal roles in the resilience and action of antidepressant drugs, making them prominent targets in psychiatric research. Oxidative stress (OS) contributes to various neurological disorders, including neurodegenerative diseases, stroke, and mental illnesses, and exacerbates the aging process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) serves as the primary cellular defense mechanism against OS-induced brain damage.

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Background: Globally, recent estimates have shown there have been 3·6 million stillbirths and neonatal deaths in 2022, with nearly 60% occurring in low-income and middle-income countries. The Small Vulnerable Newborn Consortium has proposed a framework combining preterm birth (<37 weeks of gestation), small for gestational age (SGA) by INTERGROWTH-21st standard, and low birthweight (<2500 g) under the category small vulnerable newborns (SVN). Reliable data on SVN from sub-Saharan Africa, central Asia, and south Asia are sparse.

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Introduction: Life-long adherence to gluten-free diet (GFD) and its assessment is essential for patients with celiac disease (CeD). We have developed and validated a tool for assessing adherence to GFD which can be used by both physicians and dietitians.

Methods: Phase 1: Development, content validation, and assessment of reliability of tool.

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  • Hepatitis B virus (HBV) particles are composed of HBV core protein (HBV Cp) that forms double-shelled capsids, which can spontaneously assemble under specific conditions, utilizing high ionic strength.
  • Traditional methods for studying HBV capsid assembly are complex and expensive, involving techniques like light scattering and microscopy, whereas this research introduces ProCharTS, a simpler, label-free technique that monitors real-time assembly through protein charge transfer spectra.
  • The study demonstrates that ProCharTS effectively tracks capsid formation, as the absorbance and luminescence increase during assembly, and combined with fluorescence anisotropy assays, it provides a sensitive measure of capsid characteristics compared to native dimers.
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Annual variations in animal's physiological functions are an essential strategy to deal with seasonal challenges which also vary according to the time of year. Information regarding annual adaptations in the immune-competence to cope with seasonal stressors in reptiles is scarce. The present research plan was designed to analyze the presence of circannual immune rhythms in defense responses of the leucocytes in an ophidian, Natrix piscator.

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The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated.

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Article Synopsis
  • Pancreatic β cells release insulin when blood sugar goes up to help keep glucose levels steady in the body.
  • A special protein called Vaha, found in fruit flies, is made in the gut and moves to the brain, where it helps the cells that produce insulin.
  • When there's a lot of fat in the diet, Vaha boosts the release of insulin-like peptides, and without it, the body can have problems like high blood sugar and fat levels.
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Nanomaterials are widely employed in wastewater treatment, among which nanoferrites and their composites hold significant prominence. This study adopts a green approach to synthesize zinc ferrite nanoparticles, subsequently integrating them with polyaniline (PANI) to fabricate the ZnFeO-PANI nanocomposite. Characterization of the prepared ZnFeO-PANI nanocomposite was conducted using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopic (SEM) techniques.

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  • The study aimed to evaluate reproductive functions in female patients with celiac disease (CeD), which are often overlooked.
  • It compared 288 female patients with CeD to 586 age-matched healthy controls using a detailed questionnaire about reproductive health.
  • Results showed that women with CeD experienced higher ages at menarche, abnormal menstrual patterns, delayed conception, infertility, and poorer pregnancy outcomes compared to controls, affecting about three-fourths of the CeD patients.
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Objectives: We hypothesized that crypt failure in the small bowel results in villous flattening in patients with celiac disease (CeD). We investigated whether alterations in the stem cell niche (ISC) are responsible for this phenomenon.

Materials And Methods: We included 92 duodenal (D2/3) biopsies from treatment-naive patients of CeD and 37 controls.

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