Reconnecting the roots of hydrogen sulfide (HS) with medicinal chemistry: Lessons accomplished and challenges so far.

Previously known for its unpleasant odour and mortality in elevated concentrations, hydrogen sulfide (HS) is currently considered a complex molecule having significant physiological advantages. After nitric oxide (NO) and carbon monoxide (CO), HS is regarded as the third endogenous gasotransmitter, performing many biological functions in the human body. The essential functions include but are not limited to regulating inflammation, maintaining the redox potential, cellular signalling, and metabolic processes.

Design and synthesis of new 1,4-naphthoquinones appended sulfenylated thiazoles as cyclooxygenase II inhibitors: Exploring the utility in the development of anticancer agents.

Clinical evaluations revealed the direct role of chronic inflammation in cancer progression. The cyclooxygenase (COX) pathway is particularly important among the various pathways involved in inflammation. There are two COX isoforms: COX-1 and COX-2.

Nanotechnology Assisted Drug Delivery Strategies for Chemotherapy: Recent Advances and Future Prospects.

In pursuit of the treatment of cancer, nanotechnology engineering has emerged as the simplest and most effective means, with the potential to deliver antitumor chemotherapeutics at the targeted site. Employing nanotechnology for drug delivery provides diverse nanosize particles ranging from one to a thousand nanometers. Reduced size improves drug bioavailability by increasing drug diffusion and decreasing the efflux rate.

Design and development of sulfenylated 5-aminopyrazoles as inhibitors of acetylcholinesterase and butyrylcholinesterase: exploring the implication for Aβ aggregation inhibition in Alzheimer's disease.

Current therapeutic regimens approved to treat Alzheimer's disease (AD) provide symptomatic relief by replenishing the acetylcholine levels in the brain by inhibiting AChE. However, these drugs don't halt or slow down the progression of Alzheimer's disease, which remains a major challenge. Evidence suggests a significant increase in BuChE activity with a decrease in AChE activity as the AD progresses along with the Aβ aggregation.

An indolium inspired portable colorimetric sensor for cyanide recognition in environmental samples with smartphone integration.

Cyanide is a highly hazardous and fast-acting blood agent widely used in various industries, making its monitoring crucial due to its severe impact on living organisms. Considering this, we had developed a novel indolium based low-cost and portable sensor for the colorimetric and fluorogenic detection of cyanide ions. The probe displayed a distinct visual color change and selectively exhibits a fluorogenic "turn-off" response to cyanide ions in pure aqueous medium.

Preclinical pharmacokinetics, absolute bioavailability and dose proportionality evaluation of bioactive phytochemical Withanone in rats.

Withanone (WN), a bioactive phytochemical isolated from the medicinal herb Withania somnifera, has shown multiple pharmacological and therapeutic successes, including neuroprotective and anti-cancer activities. However, detailed pharmacokinetic (PK) properties of pure WN were not well defined. Pharmacokinetic (PK) characteristics, dose proportionality, and absolute bioavailability of pure WN were explored in rats using an efficient, reliable, and sensitive LC-MS/MS assay to address this gap.

An overview of additive manufacturing strategies of enzyme-immobilized nanomaterials with application incatalysis and biomedicine.

Meticulous and bespoke fabrication of structural materials with simple yet innovative outlines along with on-demand availability is the imperative aspiration for numerous fields. The alliance between nanotechnology and enzymes has led to the establishment of an inimitable and proficient class of materials. With the advancement in the field of additive manufacturing, the fabrication of some complex biological architects is achievable with similitude to the instinctive microenvironment of the biological tissue.

The Capacity of Drug-Metabolising Enzymes in Modulating the Therapeutic Efficacy of Drugs to Treat Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma (STS) that predominantly affects children and teenagers. It is the most common STS in children (40%) and accounts for 5-8% of total childhood malignancies. Apart from surgery and radiotherapy in eligible patients, standard chemotherapy is the only therapeutic option clinically available for RMS patients.

Enhanced apoptosis and mitochondrial cell death by paclitaxel-loaded TPP-TPGS-functionalized nanoemulsion.

The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. A quality-by-design approach was applied for optimization and and characterization were performed. The TPP-TPGS-PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and GM cell cycle arrest compared with free-PTX treatment.

ACE2/ANG-(1-7)/Mas receptor axis activation prevents inflammation and improves cognitive functions in streptozotocin induced rat model of Alzheimer's disease-like phenotypes.

Activation of the renin-angiotensin system (RAS), by Angiotensin converting enzyme/Angiotensin II/Angiotensin receptor-1 (ACE/Ang II/AT1 R) axis elicits amyloid deposition and cognitive impairment. Furthermore, ACE2 induced release of Ang-(1-7) binds with the Mas receptor and autoinhibits ACE/Ang II/AT1 axis activation. Inhibition of ACE by perindopril has been reported to improve memory in preclinical settings.

Formulation and Characterization of Phytosomes as Drug Delivery System of Formononetin: An Effective Anti-Osteoporotic Agent.

Background: Formononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II classification.

Biodiversity: the overlooked source of human health.

Biodiversity is the measure of the variation of lifeforms in a given ecological system. Biodiversity provides ecosystems with the robustness, stability, and resilience that sustains them. This is ultimately essential for our survival because we depend on the services that natural ecosystems provide (food, fresh water, air, climate, and medicine).

Multiple Actions of HS-Releasing Peptides in Human β-Amyloid Expressing .

Alzheimer's disease (AD) is a debilitating progressive neurodegenerative disorder characterized by the loss of cognitive function. A major challenge in treating this ailment fully is its multifactorial nature, as it is associated with effects like deposition of Aβ plaques, oxidative distress, inflammation of neuronal cells, and low levels of the neurotransmitter acetylcholine (ACh). In the present work, we demonstrate the design, synthesis, and biological activity of peptide conjugates by coupling a HS-releasing moiety to the peptides known for their Aβ antiaggregating properties.

Nanomedicines targeting the inflammasome as a promising therapeutic approach for cell senescence.

Technological advancements in the present era have enhanced drug discovery and development. Nanomedicines are valuable pharmacotherapeutic tools against several diseases and disorders including aging related disorders. The mechanistic association between nanomedicines and molecular modulation have been investigated by many researchers.

Effectual Endeavors of Silk Protein Sericin against Isoproterenol Induced Cardiac Toxicity and Hypertrophy in Wistar Rats.

The silkworm cocoon has been used in the treatment of various ailments in different Asian countries. This research was designed to evaluate the effect of sericin on myocardial necrosis and hypertrophy in isoproterenol-challenged rats. The rats were administered with sericin (500 and 1000 mg/kg, p.

Discovery of 2,3-dihydro-1-pyrrolo[3,4-]quinolin-1-one derivatives as possible antileishmanial agents.

A series of uniquely functionalized 2,3,-dihydro-1-pyyrolo[3,4-]quinolin-1-one derivatives were synthesized in one to two steps by utilizing a post-Ugi modification strategy and were evaluated for antileishmanial efficacy against visceral leishmaniasis (VL). Among the library compounds, compound 5m exhibited potential antileishmanial activity (CC = 65.11 μM, SI = 7.

Self-Fluorescent Lone Tryptophan Nanoparticles as Theranostic Agents Against Alzheimer's Disease.

Aggregation of β-amyloid (Aβ42) peptide in the neural extracellular space leads to cellular dysfunction, resulting in Alzheimer's disease (AD). The hydrophobic core of the amyloidogenic Aβ42 peptide contains aromatic residues that play an important role in the self-assembly and subsequent aggregation of the peptide. Hence, targeting these hydrophobic core residues by potent low molecular agents can be a promising therapeutic approach toward AD.

Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings.

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood-plasma partitioning, bioavailability, dose proportionality, and gender difference in PK.

Isoformononetin, a dietary isoflavone protects against streptozotocin induced rat model of neuroinflammation through inhibition of NLRP3/ASC/IL-1 axis activation.

Aims: Isoformononetin (IFN), a methoxyl isoflavone present in most of human dietary supplements. However, being a highly potent antioxidant and anti-inflammatory molecule, its activity against neuronal oxidative stress and neuroinflammation has not been explored till now. The present study was inquested to assess the antioxidant, anti-apoptotic and anti-inflammatory activity of IFN against streptozotocin induced neuroinflammation in different brain regions of rat.

Chronic unpredictable stress negatively regulates hippocampal neurogenesis and promote anxious depression-like behavior via upregulating apoptosis and inflammatory signals in adult rats.

Psychological and physical stress play a pivotal role in etiology of anxiety and depression. Chronic psychological and physical stress modify various physiological phenomena, as a consequence of which oxidative stress, decreased neurotransmitter level, elevated corticosterone level and altered NSC homeostasis is observed. However, the precise mechanism by which chronic stress induce anxious depression and modify internal milieu is still unknown.

Piperine and Celecoxib synergistically inhibit colon cancer cell proliferation via modulating Wnt/β-catenin signaling pathway.

Background: Celecoxib (CXB), a selective COX-2 inhibitor NSAID, has exhibited prominent anti-proliferative potential against numerous cancers. However, its low bioavailability and long term exposure related cardiovascular side effects, limit its clinical application. In order to overcome these limitations, natural bioactive compounds with lower toxicity profile are used in combination with therapeutic drugs.

N-acetyl-cysteine in combination with celecoxib inhibits Deoxynivalenol induced skin tumor initiation via induction of autophagic pathways in swiss mice.

Deoxynivalenol is a trichothecene mycotoxin which naturally contaminates small grain, cereals intended for human and animal consumption. Investigations for dermal toxicity of DON has been needed and highlighted by WHO. Previous studies on dermal toxicity suggest that DON has DNA damaging potential leading to skin tumor initiation in mice skin.