A multi-modal approach to investigate Desmodium gangeticum's influence on stress-induced male infertility: In vivo, in vitro, and in silico assessments.

Physical and psychological stress has an inverse relation with male libido and sperm quality. The present study investigates the potential fertility-enhancing properties of Desmodium gangeticum (DG) root extracts in male Wister rats subjected to immobilization-induced stress (SIMB). DG roots were extracted using n-hexane (HEDG), chloroform (CEDG), and water (AEDG). In the pilot study, aphrodisiac protentional was investigated at two doses (125 and 250 mg kg-1) of each extract. In the main study, the HEDG and AEDG at 125 and 250 mg kg-1 were challenged for the stress by immobilization (SIMB), for 6 h daily over 28 days. Parameters assessed included aphrodisiac effects, gonadosomatic index (GSI), semen quality, sperm quantity, fructose content, serum hormonal levels, testicular oxidative stress, and testicular histopathology. Additional in silico studies, including the lipid solubility index, molecular docking, molecular dynamics, and SymMap studies were conducted for validation. HEDG demonstrated significant aphrodisiac activity, improved - GSI, sperm quality and quantity, and fructose content, serum testosterone levels, histological changes induced by SIMB in the testes. Swiss ADME studies indicated Gangetin (a pterocarpan) had a high brain permeation index (4.81), a superior docking score (-8.22), and higher glide energy (-42.60), compared with tadalafil (-7.17). The 'Lig fit Prot' plot in molecular dynamics simulations revealed a strong alignment between Gangetin and phosphodiesterase type 5 (PDE5). HEDG exerts aphrodisiac effects by increasing blood testosterone levels and affecting PDE5 activity. The protective effects on spermatozoa-related parameters and testicular histological changes are attributed to the antioxidant and anti-inflammatory properties, of pterocarpan (gangetin).

Multi-faceted Anti-obesity Effects of N-Methyl-D-Aspartate (NMDA) Receptor Modulators: Central-Peripheral Crosstalk.

Hypothalamus is central to food intake and satiety. Recent data unveiled the expression of N-methyl-D-aspartate receptors (NMDAR) on hypothalamic neurons and their interaction with GABAA and serotoninergic neuronal circuits. However, the precise mechanisms governing energy homeostasis remain elusive. Notably, in females, the consumption of progesterone-containing preparations, such as hormonal replacement therapy and birth control pills, has been associated with hyperphagia and obesity-effects mediated through the hypothalamus. To elucidate this phenomenon, we employed the progesterone-induced obesity model in female Swiss albino mice. Four NMDAR modulators were selected viz. dextromethorphan (Dxt), minocycline, d-aspartate, and cycloserine. Obesity was induced in female mice by progesterone administration for 4 weeks. Mice were allocated into 7 groups, group-1 as vehicle control (arachis oil), group-2 (progesterone + arachis oil), and group-3 as positive-control (progesterone + sibutramine); other groups were treated with test drugs + progesterone. Various parameters were recorded like food intake, thermogenesis, serum lipids, insulin, AST and ALT levels, organ-to-body weight ratio, total body fat, adiposity index, brain serotonin levels, histology of liver, kidney, and sizing of fat cells. Dxt-treated group has shown a significant downturn in body weight (p < 0.05) by a decline in food intake (p < 0.01), organ-to-liver ratio (p < 0.001), adiposity index (p < 0.01), and a rise in body temperature and brain serotonin level (p < 0.001). Dxt demonstrated anti-obesity effects by multiple mechanisms including interaction with hypothalamic GABAA channels and anti-inflammatory and free radical scavenging effects, improving the brain serotonin levels, and increasing insulin release from the pancreatic ß-cells.

Laser activatable nanographene colloids for chemo-photothermal combined gene therapy of triple-negative breast cancer.

This investigation reports the green approach for developing laser activatable nanoscale-graphene colloids (nGC-CO-FA) for chemo-photothermal combined gene therapy of triple-negative breast cancer (TNBC). The nano colloid was found to be nanometric as characterized by SEM, AFM, and zeta sizer (68.2 ± 2.1 nm; 13.8 ± 1.2 mV). The doxorubicin (Dox) loaded employing hydrophobic interaction/π-π stacking showed >80% entrapment efficiency with a sustained pH-dependent drug release profile. It can efficiently incorporate siRNA and Dox and successfully co-localize them inside TNBC cells to obtain significant anticancer activity as evaluated using CCK-8 assay, apoptosis assay, cell cycle analysis, cellular uptake, fluorescence assay, endosomal escape study, DNA content analysis, and gene silencing efficacy studies. nGC-CO-FA/Dox/siRNA released the Dox in temperature- and a pH-responsive manner following NIR-808 laser irradiation. The synergistic photo-chemo-gene therapy using near infrared-808 nm laser (NIR-808) irradiation was found to be more effective as compared to without NIR-808 laser-treated counterparts (∆T: 37 ± 1.1 °C → to 49.2 ± 3.1 °C; 10 min; 0.5 W/cm2), suggesting the pivotal role of photothermal combined gene-therapy in the treatment of TNBC.

Recent advancements and future submissions of silica core-shell nanoparticles.

The core-shell silica-based nanoparticles (CSNPs) possess outstanding properties for developing next-generation therapeutics. CSNPs provide greater surface area owing to their mesoporous structure, which offers a high opportunity for surface modification. This review highlights the potential of core-shell silica-based nanoparticle (CSNP) based injectable nanotherapeutics (INT); its role in drug delivery, biomedical imaging, light-triggered phototherapy, Plasmonic enhancers, gene delivery, magnetic hyperthermia, immunotherapy, and potential as next-generation theragnostic. Specifically, the conceptual crosstalk on modern synthetic strategies, biodistribution profiles with a mechanistic view on the therapeutics loading and release modeling are dealt in detail. The manuscript also converses the challenges associated with CSNPs, regulatory hurdles, and their current market position.

Nanogold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynamic- therapy of rheumatoid arthritis.

This investigation reports a novel nanoGold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynamic- therapy of rheumatoid arthritis (RA). Architecturally, the nanocomposites comprised of a nanoGold (Au) at the focal whose surface is functionalized by hydroxy-terminated thiolated-dendrons following Au-thiol bond formation to produce nanoGold-core multifunctional dendrimer (Au-DEN). The surface hydroxyl groups of Au-DEN were then conjugated with methotrexate (MTX; a disease-modifying first line anti-rheumatic drug; DMARD; 74.29 ±â€¯0.48% loading) to form Au-DEN-MTX-NPs (Particle size: 100.15 ±â€¯28.36 nm; poly dispersibility index, PDI: 0.39 ±â€¯0.02; surface zeta potential, ζ: -22.45 ±â€¯1.06 mV). MTX was strategically selected to serve as an anti-rheumatic DMARD as well as a targeting ligand to attain selective localization of the formulation in arthritic tissue via folate receptors upregulated on arthritic tissues. The docking study was performed to confirm the viable binding efficiency of MTX towards ß-folate receptors that are overexpressed on arthritic tissues taking folic acid as a reference standard. The IR780, a NIR active bioactive was also loaded in Au-DEN-MTX NPs to offer photothermal benefit upon irradiation with NIR laser (wavelength: 808 nm). The hypothesis was tested by elucidation of in vitro drug release profile, photothermal activity, cellular uptake (Fluorescence and confocal laser scanning microscopy; CLSM), cell viability assay (MTT protocol) and Intracellular reactive oxygen species (ROS) generation in mouse macrophage RAW264.7 cells and Lipopolysaccharide (LPS) activated RAW264.7 cells. Furthermore, the hemolytic toxicity and stability studies were also investigated to determine the blood compatibility as well as ideal storage condition of NPs. The outcome of this investigations presents developed multifunctional targeted NPs to be potential therapeutics for the improved treatment of RA. The approach can also be applied to other clinical interventions involving countering inflammatory conditions.

Carbon nanotubes in the delivery of anticancer herbal drugs.

Cancer is estimated to be a significant health problem of the 21st century. The situation gets even tougher when it comes to its treatment using chemotherapy employing synthetic anticancer molecules with numerous side effects. Recently, there has been a paradigm shift toward the adoption of herbal drugs for the treatment of cancer. In this context, a suitable delivery system is principally warranted to deliver these herbal biomolecules specifically at the tumorous site. To achieve this goal, carbon nanotubes (CNTs) have been widely explored to deliver anticancer herbal molecules with improved therapeutic efficacy and safety. This review uniquely expounds the biopharmaceutical, clinical and safety aspects of different anticancer herbal drugs delivered through CNTs with a cross-talk on their outcomes. This review will serve as a one-stop-shop for the readers on various anticancer herbal drugs delivered through CNTs as a futuristic delivery device.