Biallelic Variant in SLC6A17 in a Pakistani Family With Autosomal Recessive Intellectual Disability.

Autosomal recessive intellectual disability affects 1%-33% of the general population and is a major concern in countries where consanguineous marriages are common. Mental retardation autosomal recessive 48 (MRT 48) (OMIM 616269) is a recessive syndromic disorder characterized by progressive tremors, speech impairment, and behavioral problems. In the present study, we highlight a family with a case of MRT 48.

Interaction between Maslinic acid and HSF1 enhances the ubiquitin degradation of HSF1, resulting in the inhibitory effect of pancreatic cancer.

Maslinic acid (MA), a pentacyclic triterpenoid, displays broad biological activity including anti-inflammatory, antihyperlipidemic, anti-tumor, cardiovascular protection etc. Our previous study has shown that MA inhibits the proliferation of pancreatic cancer cells via heat shock protein HSPA8-mediated autophagy pathway, but the detailed mechanism is still unclear. In the present study, we confirmed that MA downregulated the protein expression of the transcription factor of heat shock protein 1(HSF1), and knockdown of HSF1 was able to enhance the inhibitory effect of MA in pancreatic cancer cells.

Association of angiotensin I converting enzyme gene I/D polymorphism and coronary artery disease in the Pakistani population.

ObjectiveThe aim of this study was to investigate the association between angiotensin I converting enzyme gene polymorphism and coronary artery disease in the Pakistani population, given the early onset and aggressive nature of coronary artery disease in this region.MethodsA case-control study was conducted involving 540 Pakistani patients with established coronary artery disease and 224 healthy controls. DNA samples were amplified using polymerase chain reaction with primers targeting the insertion (I)/deletion (D) sites of intron 16 of the angiotensin I converting enzyme gene.

Association of excessive screen time exposure with ocular changes leading to astigmatism in children.

Purpose: The purpose of this study was to find the relationship between excessive screen time exposure and the development of astigmatism in children.

Methods: A cross-sectional correlational study was conducted at tertiary care hospital, Islamabad between June 2023 to May 2024. In total, 431 patients were included in this study after informed written consent.

Excessive screen time exposure leads to dry eyes and inflammatory conjunctivitis in children.

Background: The rise in usage of smartphones and digital devices among pediatric population has raised concerns about their eye's health. It is of particular interest in relation to dry eye disease (DED) and inflammatory conjunctivitis. Prolonged screen exposure is linked to reduced blink rates, tear evaporation, and tear break-up time (TBUT), that can lead to ocular discomfort and tear instability.

Recurrent Missense Driver STAT5B N642H Mutation in Children Transiting into Adolescence, with Acute Lymphoid Leukemia and its In silico Inhibition.

Background: The occurrence of gain of function mutations in STAT5B has been associated to survival, and drug resistance in Leukemia. In silico screening of compounds having inhibitory potential towards mutated proteins, can be helpful in the development of specific inhibitors.

Objective: This study was designed to screen selected JAK-STAT mutations in leukemia patients and virtual exploration of molecular interaction of potential inhibitors with their mutated products.

Morphological Features Influence the Drug Loading and Delivery Efficacy of Photoactivatable Gold Nanocarriers for Antitumor Photo/Chemotherapy.

Photoactivatable gold nanocarriers are transforming antitumor therapies by leveraging their distinctive physicochemical properties, enabling targeted drug delivery and enhanced therapeutic efficacy in cancer treatment. This study systematically investigates how surface topography and morphology of gold nanocarriers influence drug loading capacity, light-to-heat conversion efficiency, and overall therapeutic performance in photo/chemotherapy. We synthesized four distinct morphologies of gold nanoparticles: porous gold nanocups (PAuNCs), porous gold nanospheres (PAuNSs), solid gold nanocups (SAuNCs), and solid gold nanospheres (SAuNSs).

TRAIL as a Warrior in Nano-Sized Trojan Horse: Anticancer and Anti-Metastatic Effects of Nano-Formulations of TRAIL in Cell Culture and Animal Model Studies.

Cancer is a therapeutically challenging and genomically complicated disease. Pioneering studies have uncovered multifaceted aspects of cancer, ranging from intra- and inter-tumor heterogeneity, drug resistance, and genetic/epigenetic mutations. Loss of apoptosis is another critical aspect that makes cancer cells resistant to death.

High-Throughput Drug Screening in Chondrosarcoma Cells Identifies Effective Antineoplastic Agents Independent of IDH Mutation.

The term chondrosarcoma refers to a rare and heterogeneous group of malignant cartilaginous tumors that are typically resistant to chemotherapy and radiotherapy. Metastatic chondrosarcoma has a poor prognosis, and effective systemic therapies are lacking. Isocitrate dehydrogenase (IDH) mutations represent a potential therapeutic target, but IDH inhibitors alone have shown limited clinical efficacy to date.

Phytochemical, Cytoprotective Profiling, and Anti-Inflammatory Potential of in Rheumatoid Arthritis: An Experimental and Simulation Study.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first line of treatment, are associated with a range of adverse effects.

Albumin-To-Alkaline Phosphatase Ratio as a New Early Predictive Marker of Axillary Response in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Pilot Study.

The Albumin-to-Alkaline Phosphatase ratio (AAPR) is an easily applicable and cost-effective marker investigated as an outcome predictor in solid cancers. Preliminary evidence in breast cancer suggests that a low AAPR correlates with a poor response to neoadjuvant chemotherapy (NAC) in primary tumors. However, data regarding the axillary response are lacking.

Mechanistic Insights and Molecular Diagnostics of TMPRSS2-ERG: Overview of the Journey from Regulation of Signaling Landscape in Fusion Positive Prostate Cancer to Appraisal as a Diagnostic Marker.

Chromosomal rearrangements and recurrent gene fusions were previously presumed to be the primary oncogenic mechanisms of hematological malignancies. However, the discovery of gene fusions in different cancers has opened new horizons to comprehensively investigate how cell type-specific fusion oncoproteins modulate signaling cascades. Prostate cancer (PCa) is a multifaceted and therapeutically challenging disease, and functional genomics have helped us develop a better understanding of the mechanisms underlying prostate carcinogenesis, castration-resistant PCa, and metastasis.

Support Vector Machine Outperforms Other Machine Learning Models in Early Diagnosis of Dengue Using Routine Clinical Data.

There is a dire need for the establishment of active dengue surveillance to continuously detect cases, circulating serotypes, and determine the disease burden of dengue fever (DF) in the country and region. Predicting dengue PCR results using machine learning (ML) models represents a significant advancement in pre-emptive healthcare measures. This study outlines the comprehensive process of data preprocessing, model selection, and the underlying mechanisms of each algorithm employed to accurately predict dengue PCR outcomes.

Anti-metastatic Effects of Bee Venom and Melittin in Breast Cancer Cells by Upregulation of BRMS1 and DRG1 Genes.

Apitherapy has started to gain tremendous recognition because of extraordinary pharmacological importance of honeybee-related ingredients and their derivatives. There has been a renewed interest in the bee venom-based therapies. Interdisciplinary researchers are studying the chemistry and translational value of venom for effective cancer treatment.

Meridional Amblyopia and Spectacle Correction: A Prospective Interventional Study of Children Aged 4-11 Years.

Background Amblyopia, often linked to high astigmatism in children, presents challenges in understanding the contributing factors and visual outcomes. Methods A total of 132 samples were included in this prospective pre- and post-interventional study using the purposive sampling technique. Descriptive statistics were applied for age, gender, uncorrected visual acuity, corrected visual acuity, type, and magnitude of astigmatism.

Interplay between JAK/STAT pathway and non-coding RNAs in different cancers.

Progress in the identification of core multi-protein modules within JAK/STAT pathway has enabled researchers to develop a better understanding of the linchpin role of deregulated signaling cascade in carcinogenesis and metastasis. More excitingly, complex interplay between JAK/STAT pathway and non-coding RNAs has been shown to reprogramme the outcome of signaling cascade and modulate immunological responses within tumor microenvironment. Wealth of information has comprehensively illustrated that most of this complexity regulates the re-shaping of the immunological responses.

Role of melatonin in carcinogenesis and metastasis: From mechanistic insights to intermeshed networks of noncoding RNAs.

In recent years, seminal studies have been devoted to unraveling the puzzling mysteries associated with the cancer preventive/inhibitory role of melatonin. Our current knowledge of the translational mechanisms and the detailed structural insights have highlighted the characteristically exclusive role of melatonin in the inhibition of carcinogenesis and metastatic dissemination. This mini-review outlines recent discoveries related to mechanistic role of melatonin in prevention of carcinogenesis and metastasis.

Role of TRP channels in carcinogenesis and metastasis: Pathophysiology and regulation by non-coding RNAs.

In 2021, David Julius and Ardem Patapoutian received Nobel Prize in Physiology or Medicine for their ground-breaking discoveries in the functional characterization of receptors for temperature and touch. Transient receptor potential (TRP) channels have captivated tremendous appreciation as promising drug targets over the past few years because of central involvement in different cancers. Based on the insights gleaned from decades of high-quality research, basic and clinical scientists have unveiled how Transient receptor potential channels regulated cancer onset and progression.

Regulation of Nrf2/Keap1 signaling pathway in cancer drug resistance by galectin-1: cellular and molecular implications.

Oxidative stress is characterized by the deregulation of the redox state in the cells, which plays a role in the initiation of various types of cancers. The activity of galectin-1 (Gal-1) depends on the cell redox state and the redox state of the microenvironment. Gal-1 expression has been related to many different tumor types, as it plays important roles in several processes involved in cancer progression, such as apoptosis, cell migration, adhesion, and immune response.

Activation of Stimulator of Interferon Genes (STING): Promising Strategy to Overcome Immune Resistance in Prostate Cancer.

Prostate cancer (PCa) is the most frequent and second-lethal cancer among men. Despite considerable efforts to explore treatments like autologous cellular immunotherapy and immune checkpoint inhibitors, their success remains limited. The intricate tumor microenvironment (TME) and its interaction with the immune system pose significant challenges in PCa treatment.

Navigating the brain: the role of exosomal shuttles in precision therapeutics.

Brain diseases have become one of the leading roots of mortality and disability worldwide, contributing a significant part of the disease burden on healthcare systems. The blood-brain barrier (BBB) is a primary physical and biological obstacle that allows only small molecules to pass through it. Its selective permeability is a significant challenge in delivering therapeutics into the brain for treating brain dysfunction.

Role of Platelet-Derived Growth Factor-mediated signaling in carcinogenesis and metastasis.

Platelet-Derived Growth Factor (PDGF) mediated signaling has emerged as one of the most extensively studied cascades in cancer development and progression. Overwhelmingly increasing data obtained from preclinical and clinical studies has helped us to develop a near-complete resolution of PDGF/PDGFR signaling landscape. Phenotype- and genotype-driven studies have provided proof-of-concept that therapeutic targeting of PDGF/PDGFR signaling axis is necessary to improve clinical outcome.

Inhibition of Ehrlich ascites carcinoma growth by melatonin: Studies with micro-CT.

Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling pathway. Melatonin has many benefits, such as organizing circadian rhythms and acting as a powerful hormone. We aimed to show the antitumor effects of melatonin in both and models through the mammalian target of rapamycin (mTOR) signaling pathway and the Argyrophilic Nucleolar Regulatory Region (AgNOR), using the Microcomputed Tomography (Micro CT).

Novel 2D MXene Cobalt Ferrite (CoF@TiC) Composite: A Promising Photothermal Anticancer In Vitro Study.

In search of materials with superior capability of light-to-heat (photothermal) conversion, biocompatibility, and confinement of active photothermal materials within the cells, novel magnetic MXene-based nanocomposites are found to possess all of these criteria. The CoF@TiC composite is fabricated by a simple two-step method, including an exfoliation strategy followed by sonochemical method. MXene composite has been modified with polyvinylpyrrolidone (PVP) to improve the stability in physiological conditions.