Amorphization of Low Soluble Drug with Amino Acids to Improve Its Therapeutic Efficacy: a State-of-Art-Review.

Low aqueous solubility of drug candidates is an ongoing challenge and pharmaceutical manufacturers pay close attention to amorphization (AMORP) technology to improve the solubility of drugs that dissolve poorly. Amorphous drug typically exhibits much higher apparent solubility than their crystalline form due to high energy state that enable them to produce a supersaturated state in the gastrointestinal tract and thereby improve bioavailability. The stability and augmented solubility in co-amorphous (COA) formulations is influenced by molecular interactions. COA are excellent carriers-based drug delivery systems for biopharmaceutical classification system (BCS) class II and class IV drugs. The three important critical quality attributes, such as co-formability, physical stability, and dissolution performance, are necessary to illustrate the COA systems. New amorphous-stabilized carriers-based fabrication techniques that improve drug loading and degree of AMORP have been the focus of emerging AMORP technology. Numerous low-molecular-weight compounds, particularly amino acids such as glutamic acid, arginine, isoleucine, leucine, valine, alanine, glycine, etc., have been employed as potential co-formers. The review focus on the prevailing drug AMORP strategies used in pharmaceutical research, including in situ AMORP, COA systems, and mesoporous particle-based methods. Moreover, brief characterization techniques and the application of the different amino acids in stabilization and solubility improvements have been related.

Interplay mechanisms between progesterone and endocannabinoid receptors in regulating bull sperm capacitation and acrosome reaction.

After ejaculation, sperm show a limited capacity for transcription and translation. In the oviduct, most of the signalling in sperm is nongenomic and is mediated through membrane receptors. Studies have shown that the cation channel of sperm (CatSper), cAMP, cGMP, protein kinases, and tyrosine phosphorylation are involved in the nongenomic signalling of progesterone (P4) in sperm. However, it is not known whether there is an interplay between P4 and cannabinoid receptors 1 and 2 (CB1 and CB2), transient receptor potential vanilloid 1 (TRPV1), CatSper channels, cAMP, inositol trisphosphate receptor (IP3R), and mitogen-activated protein kinase (MAPK); these potential regulators are involved in the regulation of capacitation and the acrosome reaction. In the present study, selective blockers of CB1, CB2, TRPV1, CatSper channels, cAMP, protein kinase A (PKA), IP3R, and MAPK were used to identify their involvement in P4-mediated bull sperm capacitation and the acrosome reaction. Selective blocking of any one of the molecules caused a significant reduction in P4 signalling (p < 0.05). Interestingly, blocking these molecules in combination followed by treatment with P4 resulted in the complete absence of capacitation and the acrosome reaction. Blocking a single receptor was not able to eliminate the P4-induced capacitation and the acrosome reaction. In addition to the CB1 and CB2 receptors, there may be other signalling pathways that mediate P4 signalling. In conclusion, P4 signalling exhibited interplay with the cannabinoid receptors. The regulation of sperm capacitation and the acrosome reaction also involved cAMP, PKA, l-type and T-type calcium channels, TRPV1, inositol trisphosphate, and MAPK.

Curcumin in a tris-based semen extender improves cryosurvival of Hariana bull spermatozoa.

In this study, the cryoprotective potential of natural antioxidant curcumin in Hariana bull semen was evaluated as an additive in a tris-based extender with the assessment of motility and motion parameters of spermatozoa, membrane intactness, progesterone-receptor binding, protein carbonyl content, cervical mucus penetration, cryocapacitation-associated and apoptotic-like changes. The collected ejaculates were divided into five groups in the tris-based extender (control without curcumin-I, 10 µM-II, 25 µM-III, 50 µM-IV and 75µM-V) and were cryopreserved. Groups II and III containing 10 and 25 µM curcumin substantially (p < .05) improved the post-thaw sperm parameters like viability, motility, and velocity parameters; intact acrosome and membrane; lowered protein carbonyl content; DNA fragmentation and cryocapacitation-associated changes in comparison to control. It was interesting to note that early apoptotic-like changes in sperm cells were significantly (p < .05) decreased in Group II along with an increase in a higher population of sperm cells having high mitochondrial transmembrane potential. Higher progesterone-receptor binding, Vanguard distance and in vitro capacitation response were observed only in Group II (10µM) compared to other groups. In conclusion, curcumin in a semen extender manifests cryoprotective effects and may be incorporated at 10 µM concentration in a Hariana bull semen extender for better post-thaw sperm quality.

Phytoremediation mechanism and role of plant growth promoting rhizobacteria in weed plants for eco-restoration of hazardous industrial waste polluted site: a review.

Plants have numerous strategies for phytoremediation depending upon the characteristic of pollutants. Plant growth promoting rhizobacteria (PGPR) are essential to the process of phytoremediation and play a key part in it. The mechanism of PGPR for phytoremediation is mediated by two methods; under the direct method there is phytohormone production, nitrogen fixation, nutrient mineral solubilization, and siderophore production while the indirect method includes quorum quenching, antibiosis, production of lytic enzyme, biofilm formation, and hydrogen cyanide production. Due to their economic and environmental viability, most researchers have recently concentrated on the potential of weed plants for phytoremediation. Although weed plants are considered unwanted and noxious, they have a high growth rate and adaptability which opens a high scope for its role in phytoremediation of contaminated site. The interaction of plant with rhizobacteria starts from root exudates containing various organic acids and peptides which act as nutrients essential for colonization and siderophore production by the rhizospheric bacteria. The rhizobacteria, while colonizing, tend to promote plant growth and health either directly by providing phytohormones and minerals or indirectly by suppressing growth of possible phytopathogens. Recently, several weed plants have been reported for phytoextraction of heavy metals (Ni, Pb, Zn, Hg, Cd, Cu, As, Fe, and Cr) contaminants from various agro-based industries. These potential native weed plants have high prospect of eco-restoration of polluted site with complex organo-metallic waste for sustainable development.

Antioxidant additive melatonin in tris-based egg yolk extender improves post-thaw sperm attributes in Hariana bull.

In the study, melatonin, a known antioxidant pineal peptide was used as an additive in the tris-egg yolk glycerol-based semen extender in Hariana bull semen and post-thaw sperm characters were evaluated. In the study, Group I was a control without melatonin; and Group II, III, and IV were having 0.5 mM, 1 mM, and 2 mM melatonin/80 × 106 spermatozoa, respectively were treatment groups. Thirty-two semen ejaculates from 4 Hariana bulls were processed for freezing and post-thaw sperm characteristics were evaluated. Sperm motility, velocity, the viability with intact membrane, and total antioxidant capacity were markedly (P < 0.05) improved in Group IV compared to all other groups. The lipid peroxidation and total protein carbonylation were substantially (P < 0.05) decreased in Group IV compared to all other groups. The population of cryocapacitated, acrosome-reacted, and apoptotic-like spermatozoa were significantly (P < 0.05) decreased in Group IV. Further, the relative band intensity of 74 kDa protein and percent of spermatozoa showing positive immune reactivity to tyrosine-phosphorylated proteins was decreased in Group IV. The progesterone-receptor ligand binding, in vitro capacitation response, and Vanguard distance were markedly (P < 0.05) improved in Group IV. In summary- Group IV having 2 mM melatonin was found to be optimal in providing cryoprotective effects to Hariana bull spermatozoa after freezing-thawing and can be suitably used as a semen additive during semen cryopreservation.

Covid-19 Vaccines Available in India.

The present review covers the list of approved vaccines available in India, i.e., Covaxin, Covishield, and Sputnik-V. Covaxin's code name is BBV152. Covaxin was prepared by Hyderabad- based Bharat Biotech International Ltd. in collaboration with the National Institute of Virology (NIV) and ICMR. The effectiveness of Covaxin was found to be 78-81%. Covishield, which is available by code name AZD1222, was developed by the SII, Oxford University, and AstraZeneca. Covishield's effectiveness was found to be 90%. The time gap between the two doses of Covaxin and Covishiled is 4-6 weeks and 12-16 weeks, respectively. One more vaccine, i.e., Sputnik V, by the code name rAd26-S and rAd5-S, was developed by Gamaleya Research Institute of Epidemiology and Microbiology, which involves an interval gap of 21 days between the two doses. Covaxin releases Anti-SARS-CoV-2 IgG, which is specific to RBD (receptor-binding domain) protein, whereas a high degree of antibody response dissipates on the 28th day of vaccination. The protective efficacy of Sputnik-V was found to be ±92.2% (95% CI ±82.6-92.3), while that of Covishield was found to be ±90 % (95% CI 68.2-98.0±, p = 0.01) 2-standard dose: (61.2%, 95% CI 42.2-76.1±). In the case of Covaxin, the rate of seroconversion was found to be 93.9% (95% CI 85.2-98.2) in the 3-µg group and 97.2% (95% CI 93.1-105.1) in the 6-µg group. No significant difference was observed in local or systemic adverse reactions of the vaccine in the groups of 3 µg and 6 µg. The protective efficacious dose of Covaxin has not yet been identified. The cellular response median SFCs PBPMC of Covishield at the standard dose in the age group of 18-55 years was found to be±1201; 55-70 years: ±758 and ≥75 years: ±975. No significant increase was observed in the per million peripheral mononuclear cells (PBPMC) after administration of the booster dose of Covishield vaccine (p = 0.45 in paired student's t-test on the 28th day vs. the 42nd day). The cellular response to Sputnik V was found to be 100%. Higher levels of T cells CD8+, CD4+ T cells, and IFN- γ secretion were reported in all volunteers who had undergone vaccination. Cell proliferation was found as follows: CD4+: +1.5% and CD8+ : +1.3% in the lyophilized formulation and CD4+ : + 2.6% and CD8+ : +1.5% in the frozen formulation. Antigen-specific IgG geometric mean titer (GMT) levels of Covishield were found to be highest on the 28th day with 160 geometric mean ELISA units (GMEU).

Introduction to the pathways involved in the activation and regulation of sperm motility: A review of the relevance of ion channels.

To participate in sperm-oocyte fusion, spermatozoa need to be motile. In the testes, spermatozoa are immotile, although these gametes acquire the capacity for motility during the transit through the epididymis. During the period of epididymal transport from the male genital tract to the female genital tract, spermatozoa exhibit various types of motility that are regulated by complex signalling and communication mechanisms. Because motility is very dynamic, it can be affected by small changes in the external or internal environment of spermatozoa within a very short time. This indicates that regulatory membrane proteins, known as sperm ion channels, are involved in the regulation of sperm motility. Research results from studies, where there was use of electrophysiological, pharmacological, molecular and knock-out approaches, indicate ion channels are possibly involved in the regulation of sperm membrane polarisation, intracellular pH, motility, energy homeostasis, membrane integrity, capacitation, hyperactivity, acrosome reaction and fertilisation processes. In this review, there is summarisation of the key functions that ion channels have in the regulation, initiation, maintenance, and modulation of sperm motility. In addition, in this review there is highlighting of novel insights about the pathways of ion channels that are activated in spermatozoa while these gametes are located in the oviduct leading to the fertilisation capacity of these cells.