Recent advances in developing targeted protein degraders.

Targeted protein degradation (TPD) represents a promising therapeutic approach, encompassing several innovative strategies, including but not limited to proteolysis targeting chimeras (PROTACs), molecular glues, hydrophobic tag tethering degraders (HyTTD), and lysosome-targeted chimeras (LYTACs). Central to TPD are small molecule ligands, which play a critical role in mediating the degradation of target proteins. This review summarizes the current landscape of small molecule ligands for TPD molecules.

IUPHAR review: Targeted therapies of signaling pathways based on the gut microbiome in autism spectrum disorders: Mechanistic and therapeutic applications.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by impairments in social interaction, communication and repetitive activities. Gut microbiota significantly influences behavior and neurodevelopment by regulating the gut-brain axis. This review explores gut microbiota-influenced treatments for ASD, focusing on their therapeutic applications and mechanistic insights.

Isolation, Structure Elucidation, and Bioactivity Evaluation of Two Alkaloids From H. Stem: A Traditional Medicinal Spice and Its Chemico-Pharmacological Aspects.

Bangladesh is endowed with an abundance of excellent medicinal plant resources. A well-known traditional medicinal plant H. from the Piperaceae family is rich in bioactive phytochemicals that have antidiarrheal, antimicrobial, analgesic, antioxidant, anticancer, and cytotoxic effects.

Phyto-pharmacological wonders of genus : Ethnopharmacological insights and phytochemical treasures from natural products.

Natural products have perennially served as a cornerstone for the genesis of novel medicinal compounds. Most clinical therapeutics originate from ancestral herbal remedies and their formulations. Scholars and practitioners have always aimed to extract better remedies to treat various ailments.

Exosome-based therapies for inflammatory disorders: a review of recent advances.

Exosomes, small extracellular vesicles secreted by cells, have emerged as focal mediators in intercellular communication and therapeutic interventions across diverse biomedical fields. Inflammatory disorders, including inflammatory bowel disease, acute liver injury, lung injury, neuroinflammation, and myocardial infarction, are complex conditions that require innovative therapeutic approaches. This review summarizes recent advances in exosome-based therapies for inflammatory disorders, highlighting their potential as diagnostic biomarkers and therapeutic agents.

Indian Shot ( L). Leaves Provide Valuable Insights into the Management of Inflammation and Other Associated Disorders Offering Health Benefits.

Background: Throughout history, plants have played a crucial role in advancing medicinal treatments by providing a diverse range of compounds for the development of innovative therapies. L. a tropical herb of the Cannaceae family, also known as Indian shot, has a rich history of traditional use in treating ailments like inflammation, malaria, dysentery, fever, dropsy, and diarrhea.

Small molecule inhibitors targeting PD-L1, CTLA4, VISTA, TIM-3, and LAG3 for cancer immunotherapy (2020-2024).

Cancer immunotherapy, leveraging antibodies, excels in targeting efficacy but faces hurdles in tissue penetration, oral delivery, and prolonged half-life, with costly production and risk of adverse immunogenic effects. In contrast, small molecule immuno-oncology agents provide favorable pharmacokinetic properties and benign toxicity profiles. These agents are well-positioned to address the limitations of antibody-based immunotherapies, augment existing treatment modalities, and achieve synergistic effects when combined with antibodies.

Unveiling the Therapeutic Potentials of Water Hyacinth (Eichhornia crassipes (Mart.) Solms) Flower against Oxidative Stress, Inflammation and Depressive Disorders: GC-MS/MS, In Vitro, In Vivo and In Silico Approaches.

Water hyacinth (Eichhornia crassipes (Mart.) Solms) is a highly invasive aquatic weed native to the Amazonia basin, known for its rapid propagation, adaptability, and utilization in traditional medicine. The study aims to unveil the therapeutic potential of water hyacinth flowers methanolic extract (EC CME) and its four kupchan fractions (EC PESF, EC DCMSF, EC EASF, EC ASF) through diversified chemical-pharmacological approaches.

MRI Radiomics Combined with Clinicopathological Factors for Predicting 3-Year Overall Survival of Hepatocellular Carcinoma After Hepatectomy.

Background: A limited number of studies have examined the use of radiomics to predict 3-year overall survival (OS) after hepatectomy in patients with hepatocellular carcinoma (HCC). This study develops 3-year OS prediction models for HCC patients after liver resection using MRI radiomics and clinicopathological factors.

Materials And Methods: A retrospective analysis of 141 patients who underwent surgical resection of HCC was performed.

Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306).

Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.

Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG).

Pyroptosis in Diabetic Peripheral Neuropathy and its Therapeutic Regulation.

Pyroptosis is a pro-inflammatory form of cell death resulting from the activation of gasdermins (GSDMs) pore-forming proteins and the release of several pro-inflammatory factors. However, inflammasomes are the intracellular protein complexes that cleave gasdermin D (GSDMD), leading to the formation of robust cell membrane pores and the initiation of pyroptosis. Inflammasome activation and gasdermin-mediated membrane pore formation are the important intrinsic processes in the classical pyroptotic signaling pathway.

Recent advances in molecular mechanisms of skin wound healing and its treatments.

The skin, being a multifaceted organ, performs a pivotal function in the complicated wound-healing procedure, which encompasses the triggering of several cellular entities and signaling cascades. Aberrations in the typical healing process of wounds may result in atypical scar development and the establishment of a persistent condition, rendering patients more vulnerable to infections. Chronic burns and wounds have a detrimental effect on the overall quality of life of patients, resulting in higher levels of physical discomfort and socio-economic complexities.

Discovery of Small and Bifunctional Molecules Targeting PD-L1/CD73 for Cancer Dual Immunotherapy.

In this work, a series of bifunctional PD-L1/CD73 (cluster of differentiation 73) small-molecule inhibitors were designed and synthesized. Among them, showed the strongest PD-L1 inhibitory effects with an IC of 6 nM and potent anti-CD73 activity with an IC of 0.773 μM.

Discovery of Novel Heterotricyclic Compounds as DNA-Dependent Protein Kinase (DNA-PK) Inhibitors with Enhanced Chemosensitivity, Oral Bioavailability, and the Ability to Potentiate Cancer Immunotherapy.

In this work, a novel series of heterotricyclic DNA-PK inhibitors were rationally designed, synthesized, and assessed for their biological activity. In the DNA-PK biochemical assay, most compounds displayed potent enzymatic activity, with IC values between 0.11 and 71.

Phyto-pharmacological evaluation and characterization of the methanolic extract of the Müll. Arg. seed: promising insights into its therapeutic uses.

Plants and their extracts have been integral to the development of medicinal treatments throughout history, offering a vast array of compounds for innovative therapies. Müll. Arg.

The Mechanism of Pyroptosis and Its Application Prospect in Diabetic Wound Healing.

Pyroptosis defines a form of pro-inflammatory-dependent programmed cell death triggered by gasdermin proteins, which creates cytoplasmic pores and promotes the activation and accumulation of immune cells by releasing several pro-inflammatory mediators and immunogenic substances upon cell rupture. Pyroptosis comprises canonical (mediated by Caspase-1) and non-canonical (mediated by Caspase-4/5/11) molecular signaling pathways. Numerous studies have explored the contributory roles of inflammasome and pyroptosis in the progression of multiple pathological conditions such as tumors, nerve injury, inflammatory diseases and metabolic disorders.

mTOR inhibitor reduces nontumour-related death in liver transplantation for hepatocellular carcinoma.

Sirolimus is a regularly applied immunosuppressant for patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Sirolimus not only significantly inhibits HCC recurrence but also protects renal function. However, the improvement effect of sirolimus on nontumour-related death in patients is still unknown.

Polyphenols Targeting NF-κB Pathway in Neurological Disorders: What We Know So Far?

Polyphenolic compounds have shown promising neuroprotective properties, making them a valuable resource for identifying prospective drug candidates to treat several neurological disorders (NDs). Numerous studies have reported that polyphenols can disrupt the nuclear factor kappa B(NF-κB) pathway by inhibiting the phosphorylation or ubiquitination of signaling molecules, which further prevents the degradation of IκB. Additionally, they prevent NF-κB translocation to the nucleus and pro-inflammatory cytokine production.

A novel nomogram for prognosis stratification in salvage liver transplantation: a national-wide study with propensity score matching analysis in China.

Background: Salvage liver transplantation (SLT) has been reported to be an efficient treatment option for patients with recurrent hepatocellular carcinoma (HCC) after liver resection (LR). However, for recipients who underwent liver transplantation (LT) due to recurrent HCC after LR in China, the selection criteria are not well established.

Methods: In this study, data from the China Liver Transplant Registry (CLTR) of 4,244 LT performed from January 2015 to December 2019 were examined, including 3,498 primary liver transplantation (PLT) and 746 SLT recipients.