Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Development of Simultaneous HPTLC Method and Validation for the Quality Assessment of Ayurvedic Formulation-Ayush Kvatha Churna by Using Marker Compound Rosmarinic Acid, Trans-Cinnamaldehyde and Piperine.

Ayurveda emphasizes the propagation of nature in maintaining health. In the present scenario, we have seen the faith of people in herbal drugs during the Covid 19 outbreak. The raises in the number of peoples have been using herbal drugs to boost immunity against infectious diseases shows the popularity of this ancient system of medicine. The standardization of Ayush Kvatha Churna (AKC), work set out to establish a straightforward, accurate and sensitive HPTLC method for the identification and quantification of marker compounds. The Rosmarinic acid, trans-Cinnamaldehyde and Piperine were used for the estimation of markers in Ayush Kvatha Churna by using HPTLC with a solvent system, consisting of Toluene: Ethyl acetate: Ethyl alcohol: Formic acid (5.6:2.4:2: 0.3 v/v/v/v). The Rf value 0.33 for Rosmarinic Acid, 0.69 for Piperine and 0.77 for trans-Cinnamaldehyde was observed and it is exactly complying with the corresponding bands in Ayush Kvatha Churna. The technique has been effectively verified and validated, enabling it to be used for the standardization or quantitative analysis of Rosmarinic acid, trans-Cinnamaldehyde and piperine in Ayush Kvatha Churna.

Nano zinc oxide mediated resuscitation of aged Cajanus cajan via modulating aquaporin, cell cycle regulatory genes and hormonal responses.

KEY MESSAGE: Nanoparticle pretreatment improved the health of aged Cajanus cajan seeds viz., regulation of redox status, gene expression, and restoration of hormonal homeostasis. Ageing deteriorates the quality of seeds by lowering their vigor and viability, and terminating with loss of germination. These days, nanotechnology has been seen to revolutionize the agricultural sectors, and particularly nano zinc oxide (nZnO) has gained considerable interests due to its distinctive properties. The aim of the present work was to decipher the possibilities of using nZnO to rejuvenate accelerated aged (AA) seeds of Cajanus cajan. Both chemically (CnZnO) and green (GnZnO; synthesized using Moringa oleifera) fabricated nZnOs were characterized via standard techniques to interpret their purity, size, and shape. Experimental results revealed erratic germination with a decline in viability and membrane stability as outcomes of reactive oxygen intermediate (ROI) buildup in AA seeds. Application of nZnO substantially rebated the accrual of ROI, along with enhanced production of antioxidants, α-amylase activity, total sugar, protein and DNA content. Higher level of zinc was assessed qualitatively/ histologically and quantitatively in nZnO pulsed AA seeds, supporting germination without inducing toxicity. Meantime, augmentation in the gibberellic acid with a simultaneous reduction in the abscisic acid level were noted in nZnO invigorated seeds than that determined in the AA seeds, suggesting possible involvement of ROI in hormonal signalling. Furthermore, nZnO-subjected AA seeds unveiled differential expression of aquaporins and cell cycle regulatory genes. Summarizing, among CnZnO and GnZnO, later one holds better potential for a revival of AA seeds of Cajanus cajan by providing considerable tolerance against ageing-associated deterioration via recouping the cellular redox homeostasis, hormonal signaling, and alteration in expression patterns of aquaporin and cell cycle regulatory genes.

Phytochemical profile and hepatoprotective potentiality of Phyllanthus genus: a review.

The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as 'Bhumyamalaki' (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future.

Understanding gut microbiome-based machine learning platforms: A review on therapeutic approaches using deep learning.

Human beings possess trillions of microbial cells in a symbiotic relationship. This relationship benefits both partners for a long time. The gut microbiota helps in many bodily functions from harvesting energy from digested food to strengthening biochemical barriers of the gut and intestine. But the changes in microbiota composition and bacteria that can enter the gastrointestinal tract can cause infection. Several approaches like culture-independent techniques such as high-throughput and meta-omics projects targeting 16S ribosomal RNA (rRNA) sequencing are popular methods to investigate the composition of the human gastrointestinal tract microbiota and taxonomically characterizing microbial communities. The microbiota conformation and diversity should be provided by whole-genome shotgun metagenomic sequencing of site-specific community DNA associating genome mapping, gene inventory, and metabolic remodelling and reformation, to ease the functional study of human microbiota. Preliminary examination of the therapeutic potency for dysbiosis-associated diseases permits investigation of pharmacokinetic-pharmacodynamic changes in microbial communities for escalation of treatment and dosage plan. Gut microbiome study is an integration of metagenomics which has influenced the field in the last two decades. And the incorporation of artificial intelligence and deep learning through "omics-based" methods and microfluidic evaluation enhanced the capability of identification of thousands of microbes.

A Review on Molecular Docking As an Interpretative Tool for Molecular Targets in Disease Management.

One of the most often utilized methods for drug discovery is molecular docking. With docking, one may discover new therapeutically relevant molecules by targeting the molecule and predicting the target-ligand interactions as well as different conformation of ligand at various positions. The prediction signifies the effectiveness of the molecule or the developed molecule having different affinity with target. Drug discovery plays an important role in the development of a new drug molecule of different moiety attached to it, which leads us in the management of several diseases. In silico approach led us to identification of numerous diseases caused by virus, fungi, bacteria, protozoa, and other microorganisms that affect human health. By means of computational approach, we can categorize disease symptoms and use the drugs available for such types of warning signs. After the docking process, molecular dynamics computational technique helps in the simulation of the physical movement of atoms and molecules for a fixed period of time, giving a view of the dynamic evaluation of the system. This review is an attempt to illustrate the role of molecular docking in drug development.

Emerging Role of Plant-Based Bioactive Compounds as Therapeutics in Parkinson's Disease.

Neurological ailments, including stroke, Alzheimer's disease (AD), epilepsy, Parkinson's disease (PD), and other related diseases, have affected around 1 billion people globally to date. PD stands second among the common neurodegenerative diseases caused as a result of dopaminergic neuron loss in the midbrain's substantia nigra regions. It affects cognitive and motor activities, resulting in tremors during rest, slow movement, and muscle stiffness. There are various traditional approaches for the management of PD, but they provide only symptomatic relief. Thus, a survey for finding new biomolecules or substances exhibiting the therapeutic potential to patients with PD is the main focus of present-day research. Medicinal plants, herbal formulations, and natural bioactive molecules have been gaining much more attention in recent years as synthetic molecules orchestrate a number of undesired effects. Several in vitro, in vivo, and in silico studies in the recent past have demonstrated the therapeutic potential of medicinal plants, herbal formulations, and plant-based bioactives. Among the plant-based bioactives, polyphenols, terpenes, and alkaloids are of particular interest due to their potent anti-inflammatory, antioxidant, and brain-health-promoting properties. Further, there are no concise, elaborated articles comprising updated mechanism-of-action-based reviews of the published literature on potent, recently investigated (2019-2023) medicinal plants, herbal formulations, and plant based-bioactive molecules, including polyphenols, terpenes, and alkaloids, as a method for the management of PD. Therefore, we designed the current review to provide an illustration of the efficacious role of various medicinal plants, herbal formulations, and bioactives (polyphenols, terpenes, and alkaloids) that can become potential therapeutics against PD with greater specificity, target approachability, bioavailability, and safety to the host. This information can be further utilized in the future to develop several value-added formulations and nutraceutical products to achieve the desired safety and efficacy for the management of PD.

Preclinical study models of psoriasis: State-of-the-art techniques for testing pharmaceutical products in animal and nonanimal models.

Local and systemic treatments exist for psoriasis, but none can do more than control its symptoms because of its numerous unknown mechanisms. The lack of validated testing models or a defined psoriatic phenotypic profile hinders antipsoriatic drug development. Despite their intricacy, immune-mediated diseases have no improved and precise treatment. The treatment actions may now be predicted for psoriasis and other chronic hyperproliferative skin illnesses using animal models. Their findings confirmed that a psoriasis animal model could mimic a few disease conditions. However, their ethical approval concerns and inability to resemble human psoriasis rightly offer to look for more alternatives. Hence, in this article, we have reported various cutting-edge techniques for the preclinical testing of pharmaceutical products for the treatment of psoriasis.

Novel Biotherapeutics Targeting Biomolecular and Cellular Approaches in Diabetic Wound Healing.

Wound healing responses play a major role in chronic inflammation, which affects millions of people around the world. One of the daunting tasks of creating a wound-healing drug is finding equilibrium in the inflammatory cascade. In this study, the molecular and cellular mechanisms to regulate wound healing are explained, and recent research is addressed that demonstrates the molecular and cellular events during diabetic wound healing. Moreover, a range of factors or agents that facilitate wound healing have also been investigated as possible targets for successful treatment. It also summarises the various advances in research findings that have revealed promising molecular targets in the fields of therapy and diagnosis of cellular physiology and pathology of wound healing, such as neuropeptides, substance P, T cell immune response cDNA 7, miRNA, and treprostinil growth factors such as fibroblast growth factor, including thymosin beta 4, and immunomodulators as major therapeutic targets.

Fluro-Protein C-Phycocyanin Docked Silver Nanocomposite Accelerates Cell Migration through NFĸB Signaling Pathway.

Currently, there is a great demand for the development of nanomedicine aided wound tissue regeneration via silver doped nanoceuticals. Unfortunately, very little research is being carried out on antioxidants-doped silver nanometals and their interaction on the signaling axis during the bio-interface mechanism. In this study, c-phycocyanin primed silver nano hybrids (AgcPCNP) were prepared and analyzed for properties such as cytotoxicity, metal decay, nanoconjugate stability, size expansion, and antioxidant features. Fluctuations in the expression of marker genes during cell migration phenomena in in vitro wound healing scenarios were also validated. Studies revealed that physiologically relevant ionic solutions did not exhibit any adverse effects on the nanoconjugate stability. However, acidic, alkali, and ethanol solutions completely denatured the AgcPCNP conjugates. Signal transduction RT2PCR array demonstrated that genes associated with NFĸB- and PI3K-pathways were significantly (p < 0.5%) altered between AgcPCNP and AgNP groups. Specific inhibitors of NFĸB (Nfi) and PI3K (LY294002) pathways confirmed the involvement of NFĸB signaling axes. In vitro wound healing assay demonstrated that NFĸB pathway plays a prime role in the fibroblast cell migration. In conclusion, the present investigation revealed that surface functionalized AgcPCNP accelerated the fibroblast cell migration and can be further explored for wound healing biomedical applications.

Phytochemicals of Cocculus hirsutus deciphered SARS-CoV-2 inhibition by targeting main proteases in molecular docking, simulation, and pharmacological analyses.

The COVID-19 pandemic is spreading rapidly due to the outbreak of novel coronavirus SARS-CoV-2 across the globe. Anti-COVID-19 drugs are urgently required in this situation. In this regard, the discovery of promising new anti-COVID-19 moieties is expected from traditional medicine. The study is aimed to discover phytochemicals of Cocculus hirsutus having anti-COVID-19 activity via inhibiting main proteases of SARS-CoV-2. Main proteases (Mpro) of SARS-CoV-2 serve as a protuberant target for anti-COVID-19 drug discovery because it is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription that makes it an attractive drug target. Recent studies indicated the utility of C. hirsutus in the treatment of viral disorders like Dengue. Phytochemicals from C. hirsutus were docked against SARS-CoV-2 main proteases (6LU7, 5R7Y, 5R7Z, 5R80, 5R81, 5R82) using the PyRx virtual screen tool and discovery studio visualizer. Further, molecular dynamics simulations were performed (for 100 ns) to see conformational stability for all complexes. Pharmacokinetic properties and drug-likeness prediction of selected C. hirsutus phytoconstituents were also performed. Betulin, coclaurine, and quinic acid of C. hirsutus were found promising with significant binding affinity to SARS-CoV-2 Mpro in comparison to control. They have shown stable interactions with the amino acid residues present on the active site of most of the SARS-CoV-2 Mpro and were found as promising anti-COVID-19 candidates. These compounds could be potential leads for the development of target-specific anti-COVID-19 therapeutics while ethnomedicinal uses of this herb could further needed for its detailed antiviral therapeutic exploration.Communicated by Ramaswamy H. Sarma.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Relevance of Solidification Kinetics for Enhanced Thermoelectric Performance in Al-Doped Higher Manganese Silicides.

The solidification kinetics of an alloy from its liquid state forms an underlying basis for microstructural engineering, wherein the state of thermodynamic equilibrium associated with the melt-grown crystal and the quenched amorphous solid denotes the two limits for crystallinity in the alloy synthesis. In this study, we report the implication of the crystalline state on the thermal and electrical transport properties of partially substituted Mn(Si1-xAlx)γ by comparing the single crystals melt-grown by the Bridgman method, and polycrystals synthesized from melt spinning (MS) and subsequent spark plasma sintering (SPS). The rapidly solidified alloys exhibited nanocrystalline microstructures in MS ribbons, while melt-grown single crystals displayed characteristics evolution of MnSi striations with limited solubility of Al. It was observed that Al as a p-type dopant enhances the carrier concentration and electrical conductivity, while nanocrystallinity in MS + SPS polycrystals and secondary phases in monocrystals were effective in enhancing the phonon scattering. Maximum zT values of ∼0.54 (±0.05) at 823 K and 0.75 (±0.05) at 873 K were attained for the single crystal (directed perpendicular to the c-axis) and melt-spun polycrystals (along the in-plane direction), respectively. These results present the efficacy of aliovalent Al substitution and demonstrate the critical role of the solidification kinetics in optimizing the carrier concentration and enhancing the phonon scattering in higher manganese silicide crystals for thermoelectric applications.

Low Lattice Thermal Conductivity in a Wider Temperature Range for Biphasic-Quaternary (Ti,V)CoSb Half-Heusler Alloys.

Intrinsically high lattice thermal conductivity has remained a major bottleneck for achieving a high thermoelectric figure of merit (zT) in state-of-the-art ternary half-Heusler (HH) alloys. In this work, we report a stable n-type biphasic-quaternary (Ti,V)CoSb HH alloy with a low lattice thermal conductivity κL ≈ 2 W m-1 K-1 within a wide temperature range (300-873 K), which is comparable to the reported nanostructured HH alloys. A solid-state transformation driven by spinodal decomposition upon annealing is observed in Ti0.5V0.5CoSb HH alloy, which remarkably enhances phonon scattering, while electrical properties correlate well with the altering electronic band structure and valence electron count (VEC). A maximum zT ≈ 0.4 (±0.05) at 873 K was attained by substantial lowering of κL and synergistic enhancement of the power factor. We perform first-principles density functional theory calculations to investigate the structure, stability, electronic structure, and transport properties of the synthesized alloy, which rationalize the reduction in the lattice thermal conductivity to the increase in anharmonicity due to the alloying. This study upholds the new possibilities of finding biphasic-quaternary HH compositions with intrinsically reduced κL for prospective thermoelectric applications.

Chemistry and anticancer activity of cardiac glycosides: A review.

The objective of this review is an attempt to emphasize the development in the chemistry and to display review of diverse therapeutic actions of cardiac glycosides. Anticancer activity of cardiac glycosides is the main activity as discussed in this review. The aim of the review is to gather the recent researches on cardiac glycosides. The present manuscript gives the platform for the researcher to have complete literature on the topic.

In Situ Evolution of Secondary Metallic Phases in Off-Stoichiometric ZrNiSn for Enhanced Thermoelectric Performance.

The full-Heusler (FH) inclusions in the half-Heusler (HH) matrix is a well-studied approach to reduce the lattice thermal conductivity of ZrNiSn HH alloy. However, excess Ni in ZrNiSn may lead to the in situ formation of FH and/or HH alloys with interstitial Ni defects. The excess Ni develops intermediate electronic states in the band gap of ZrNiSn and also generates defects to scatter phonons, thus providing additional control to tailor electronic and phonon transport properties synergistically. In this work, we present the implication of isoelectronic Ge-doping and excess Ni on the thermoelectric transport of ZrNiSn. The synthesized ZrNi1.04Sn1-xGex (x = 0-0.04) samples were prepared by arc-melting and spark plasma sintering, and were extensively probed for microstructural analysis. The in situ evolution of minor secondary phases, i.e., FH, Ni-Sn, and Sn-Zr, primarily observed post sintering resulted in simultaneous optimization of the electrical power factor and lattice thermal conductivity. A ZT of ∼1.06 at ∼873 K was attained, which is among the highest for Hf-free ZrNiSn-based HH alloys. Additionally, ab initio calculations based on density functional theory (DFT) were performed to provide comparative insights into experimentally measured properties and understand underlying physics. Further, mechanical properties were experimentally extracted to determine the usability of synthesized alloys for device fabrication.

COVID-19: clinical presentation and detection methods.

The unending outburst of COVID-19 has reinforced the necessity of SARS-CoV-2 identification approaches for the prevention of infection transmission and the proper care of severe and critical patients. As there is no cure, a prompt and reliable diagnosis of SARS-CoV2 is vital to counter the spread and to provide adequate care and treatment for the infection. Currently, RT-PCR is a gold standard detection method for the qualitative and quantitative detection of viral nucleic acids. Besides, enzyme-linked immunosorbent assay is also a primarily used method for qualitative estimation of viral load. However, almost all the detection methods have their pros and cons in terms of specificity, accuracy, sensitivity, cost, time consumption, the need for sophisticated laboratories, and the requirement of skilled technical experts to carry out the detection tests. Thus, it is suggested to integrate different techniques to enhance the detection efficiency and accurateness for SARS-CoV2. This review focuses on preliminary, pre-confirmatory, and confirmatory methods of detection such as imaging techniques (chest-X-ray and chest- computed tomography), nucleic acid detection methods, serological assay methods, and viral culture and identification methods that are currently being employed to detect the presence of SARS-CoV-2 infection along with recent detection method and applicability for COVID-19.

Plants Used as Antihypertensive.

Hypertension is a critical health problem and worse other cardiovascular diseases. It is mainly of two types: Primary or essential hypertension and Secondary hypertension. Hypertension is the primary possibility feature for coronary heart disease, stroke and renal vascular disease. Herbal medicines have been used for millions of years for the management and treatment of hypertension with minimum side effects. Over aim to write this review is to collect information on the anti-hypertensive effects of natural herbs in animal studies and human involvement as well as to recapitulate the underlying mechanisms, from the bottom of cell culture and ex-vivo tissue data. According to WHO, natural herbs/shrubs are widely used in increasing order to treat almost all the ailments of the human body. Plants are the regular industrial units for the invention of chemical constituents, they used as immunity booster to enhance the natural capacity of the body to fight against different health problems as well as herbal medicines and food products also. Eighty percent population of the world (around 5.6 billion people) consume medicines from natural plants for major health concerns. This review provides a bird's eye analysis primarily on the traditional utilization, phytochemical constituents and pharmacological values of medicinal herbs used to normalize hypertension i.e. Hibiscus sabdariffa, Allium sativum, Andrographis paniculata, Apium graveolens, Bidenspilosa, Camellia sinensis, Coptis chinensis, Coriandrum sativum, Crataegus spp., Crocus sativus, Cymbopogon citrates, Nigella sativa, Panax ginseng,Salviaemiltiorrhizae, Zingiber officinale, Tribulus terrestris, Rauwolfiaserpentina, Terminalia arjuna etc.