AI-augmented prediction of high-risk PINK1 variants associated with Parkinson's disease: integrating multilayered bioinformatics, MD simulation, and deep learning.

Parkinson's disease is a prevalent neurodegenerative disease, in which genetic mutations in many genes play an important role in its pathogenesis. Among these, a mutation in the PINK1 gene, a mitochondrial-targeted serine/threonine putative kinase 1 that protects cells from stress-induced mitochondrial dysfunction, is implicated in autosomal recessive Parkinsonism. However, the exact etiology is not well understood.

Surgical complication of SMA and celiac artery ligation during radical nephrectomy for large renal tumor: A fatal outcome.

Iatrogenic ligation of extrarenal vessels during left nephrectomy is a rarely reported yet life-threatening complication, typically occurring due to anatomical vascular variation, distorted anatomy or large lymphadenectomy. Preoperative assessment of anatomy through radiological imaging and careful identification of each vessel intraoperatively is important to prevent this complication. Such complications often result in fatal tissue ischemia and multi-organ failure if not diagnosed and managed in time.

Immunoinformatics-driven design of a multi-epitope vaccine for effective protection against Machupo virus.

The Arenaviridae family of viruses includes the Machupo virus (MACV), which is associated with the potentially fatal Bolivian hemorrhagic fever, a disease with a mortality rate of 15%-30% depending on the speed of diagnosis and the availability of health facilities. To date, there is no licensed vaccine available for MACV, highlighting the need for a preventive measure. In this work, we use immunoinformatics approaches to create a multi-epitope vaccine based on the most dominant MACV proteins.

A comprehensive systematic review of prognostic factors, survival outcomes, and the role of targeted therapies in endometrial cancer.

Study Background And Objectives: Endometrial cancer, ranking as the 6th most prevalent cancer affecting women globally, is characterized by high mortality rates, recurrence, and poor prognosis. The disease lacks comprehensive understanding and effective treatment options. This meta-analysis focuses on randomized controlled trials to investigate targeted therapies, survival outcomes, and prognostic factors in endometrial cancer.

Metastatic uterine histiocytic sarcoma: A rare presentation as solitary paraspinal mass.

Histiocytic uterine sarcoma is an extremely rare tumor with aggressive clinical course characterized by the proliferation of histiocytic cells. It is a challenging entity in terms of both diagnosis and therapy. On imaging, it has nonspecific features and a broad range of differentials, depending on regional involvement.

Targeting mRNA export complex macromolecules THO subunits (Thoc2 and Thoc5) for somatic cell reprograming.

Somatic Cell Reprogramming refers to the process of converting differentiated somatic cells back into a pluripotent state, similar to induced pluripotent stem cells (iPSCs), through molecular and cellular manipulation. This process enables biological systems to be reprogrammed for regenerative purposes. Our studies report the identification and structural prediction of the somatic cell macromolecules THO Complex Subunits 2 and 5 (Thoc2 and Thoc5).

Advancements in Structural Basis of Covalent Inhibitors Targeting SARS-CoV-2 Essential Proteins.

Covalent inhibitors play a pivotal role in the development of pharmaceutical therapies, as they form stable, irreversible bonds with target biomolecules, leading to prolonged therapeutic effects and enhanced efficacy. Since covalent inhibitors first appeared in the late 1800s, the field has become innovative rapidly, and covalent inhibitors now account for around 30% of all marketed therapeutics. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the pandemic of coronavirus disease 2019 (COVID-19).

Discovery of Small Molecule Inhibitors Targeting CTNNB1 (β-catenin) for Endometrial cancer: Employing 3D QSAR, Drug-Likeness Assessment, ADMET Predictions, Molecular Docking and Simulation.

Background: Endometrial carcinoma (EC) is a type of cancer that originates in the lining of the uterus, known as the endometrium. It is associated with various treatment options such as surgery, radiation therapy, chemotherapy, and hormone therapy, each presenting unique challenges and limitations. Beta-catenin, a protein involved in the development and progression of several cancers, including EC, plays a crucial role.

Role of small molecules as drug candidates for reprogramming somatic cells into induced pluripotent stem cells: A comprehensive review.

With the use of specific genetic factors and recent developments in cellular reprogramming, it is now possible to generate lineage-committed cells or induced pluripotent stem cells (iPSCs) from readily available and common somatic cell types. However, there are still significant doubts regarding the safety and effectiveness of the current genetic methods for reprogramming cells, as well as the conventional culture methods for maintaining stem cells. Small molecules that target specific epigenetic processes, signaling pathways, and other cellular processes can be used as a complementary approach to manipulate cell fate to achieve a desired objective.

Revolutionizing and identifying novel drug targets in via subtractive proteomics and development of a multi-epitope vaccine using reverse vaccinology and immuno-informatics.

is a gram-negative rod that has been linked to infections in people with significant comorbidities and immunocompromised immune systems. It is most commonly known to cause urinary tract infections. Thus, the development of an efficacious vaccine is imperative, as the pathogen has acquired resistance to current antibiotics.

Identification of phytochemicals as putative ligands for the targeted modulation of peroxisome proliferator-activated receptor α (PPARα) in animals.

The PPAR family of transcription factors are ligand-activated and regulate diverse functions including metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction in the body. Specifically, PPARα is known to play a role in reducing the levels of circulating triglycerides and regulating energy homeostasis in livestock animals. This study aimed to identify phytochemicals that could serve as ligands for modulation of the bovine nuclear peroxisome proliferator-activated receptor alpha (PPARα) using molecular docking studies.

Investigating In Situ Expression of Neurotrophic Factors and Partner Proteins in Irreversible Pulpitis.

Introduction: In situ assessments of neurotrophic factors and their associated molecular partners have not been explored to date, particularly in humans. The present investigation aimed to explore the expressional dysregulation of neurotrophic factors (nerve growth factor [NGF], brain derived neurotrophic factor [BDNF], and NT4/5), their receptors (TrkA and TrkB), and their modulators (USP36 and Nedd4-2) directly in irreversibly inflamed human pulp tissues.

Methods: Forty samples each of healthy and irreversibly inflamed pulp were extirpated for the study.

Identification of molecular mechanisms underlying the therapeutic effects of Celosia Cristata on immunoglobulin nephropathy.

Immunoglobulin A (IgA) nephropathy also known as Berger's disease, is a silent monster and perhaps the most prevalent glomerulonephritis that often accounts for end-stage kidney failure, thereby signifying a growing public health problem worldwide. The limited amount of available data and a broad spectrum of dysregulated physiological processes of IgAN make it a challenging task and a disproportionate economic load on the community health sector. Celosia cristata is an Amaranthaceous plant with attractive colorful inflorescences that are used in various regions of earth for the treatment of numerous ailments.

Screening of drug candidates against Endothelin-1 to treat hypertension using computational based approaches: Molecular docking and dynamics simulation.

Hypertension (HTN) is a major risk factor for cardiovascular and renal diseases, cerebrovascular accidents (CVA) and a prime underlying cause of worldwide morbidity and mortality. Hypertension is a complex condition and a strong interplay of multiple genetic, epigenetic and environmental factors is involved in its etiology. Previous studies showed an association of overexpression of genes with hypertension.

Discovery of Rift Valley fever virus natural pan-inhibitors by targeting its multiple key proteins through computational approaches.

The Rift Valley fever virus (RVFV) is a zoonotic arbovirus and pathogenic to both humans and animals. Currently, no proven effective RVFV drugs or licensed vaccine are available for human or animal use. Hence, there is an urgent need to develop effective treatment options to control this viral infection.

Designing of a multi-epitopes-based peptide vaccine against rift valley fever virus and its validation through integrated computational approaches.

Since its discovery, the Rift Valley Fever virus (RVFV) has been the source of numerous outbreaks in the Arab Peninsulas and Africa, wreaking havoc on humans and animals. The lack of therapeutics or licensed human vaccines limits the options for controlling RVFV outbreaks. Therefore, RVFV has been prioritized for rapid research and innovation of prevention strategies to control and prevent its outbreaks.

Comparative Genomic Characterization of Buffalo Fibronectin Type III Domain Proteins: Exploring the Novel Role of FNDC5/Irisin as a Ligand of Gonadal Receptors.

FN-III proteins are widely distributed in mammals and are usually involved in cellular growth, differentiation, and adhesion. The FNDC5/irisin regulates energy metabolism and is present in different tissues (liver, brain, etc.).

Designing multi-epitope vaccine against Staphylococcus aureus by employing subtractive proteomics, reverse vaccinology and immuno-informatics approaches.

Staphylococcus aureus is a deadly human bacterial pathogen that causes a wide variety of clinical manifestations. Invasive S. aureus infections in hospitals and the community are one of the main causes of mortality and morbidity, as virulent and multi-drug-resistant strains have evolved.

Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus 2 (SARS-COV-2) is a significant threat to global health security. Till date, no completely effective drug or vaccine is available to cure COVID-19. Therefore, an effective vaccine against SARS-COV-2 is crucially needed.

Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2.

Background: Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19.