Indian Society of Critical Care Medicine and Indian Association of Palliative Care Expert Consensus and Position Statements for End-of-life and Palliative Care in the Intensive Care Unit.

End-of-life care (EOLC) exemplifies the joint mission of intensive and palliative care (PC) in their human-centeredness. The explosion of technological advances in medicine must be balanced with the culture of holistic care. Inevitably, it brings together the science and the art of medicine in their full expression. High-quality EOLC in the ICU is grounded in evidence, ethical principles, and professionalism within the framework of the Law. Expert professional statements over the last two decades in India were developed while the law was evolving. Recent landmark Supreme Court judgments have necessitated a review of the clinical pathway for EOLC outlined in the previous statements. Much empirical and interventional evidence has accumulated since the position statement in 2014. This iteration of the joint Indian Society of Critical Care Medicine-Indian Association of Palliative Care (ISCCM-IAPC) Position Statement for EOLC combines contemporary evidence, ethics, and law for decision support by the bedside in Indian ICUs. How to cite this article: Mani RK, Bhatnagar S, Butola S, Gursahani R, Mehta D, Simha S, et al. Indian Society of Critical Care Medicine and Indian Association of Palliative Care Expert Consensus and Position Statements for End-of-life and Palliative Care in the Intensive Care Unit. Indian J Crit Care Med 2024;28(3):200-250.

Quinoline Derivatives as Promising Scaffolds for Antitubercular Activity: A Comprehensive Review.

BACKGROUND: Heterocyclic compounds and their derivatives play a significant role in the design and development of novel quinoline drugs. Among the various pharmacologically active heterocyclic compounds, quinolines stand out as the most significant rings due to their broad pharmacological roles, specifically antitubercular activity, and their presence in plant-based compounds. Quinoline is also known as benzpyridine, benzopyridine, and 1-azanaphthalene. It has a benzene ring fused with a pyridine ring, and both rings share two carbon atoms. The importance of quinoline lies in its incorporation as a key component in various natural compounds found in medicinal plant families like Fumariaceae, Berberidaceae, Rutaceae, Papavaraceae, and others. OBJECTIVE: This article is expected to have a significant impact on the advancement of effective antitubercular drugs. Through harnessing the potent activity of quinoline derivatives, the research aims to make valuable contributions to combating tuberculosis more efficiently and ultimately reducing the global burden of this infectious disease. METHODS: Numerous nitrogen-containing heterocyclic compounds exhibit significant potential as antitubercular agents. These chemicals have fused aromatic nitrogen-heterocyclic nuclei that can change the number of electrons they have, which can change their chemical, physical, and biological properties. This versatility comes from their ability to bind with the receptors in multiple modes, a critical aspect of drug pharmacological screening. Among these compounds, quinoline stands out as it incorporates a stable fusion of a benzene ring with a pyridine nucleus. Quinolines have demonstrated a diverse range of pharmacological activities, including but not limited to anti-tubercular, anti-tumor, anticoagulant, anti-inflammatory, antioxidant, antiviral, antimalarial, anti-HIV, and antimicrobial effects. RESULTS: Some molecules, such as lone-paired nitrogen species, include pyrrole, pyrazole, and quinoline. These molecules contain nitrogen and take part in metabolic reactions with other molecules inside the cell. However, an excessive accumulation of reactive nitrogen species can lead to cytotoxicity, resulting in damage to essential biological macromolecules. Among these compounds, quinoline stands out as the oldest and most effective one, exhibiting a wide range of significant properties such as antitubercular, antimicrobial, anti-inflammatory, antioxidant, analgesic, and anticonvulsant activities. Notably, naturally occurring quinoline compounds, such as quinine, have proven to be potent antimalarial drugs. CONCLUSION: This review highlights quinoline derivatives' antitubercular potential, emphasizing recent research advancements. Utilizing IC50 values, the study emphasizes the efficacy of various quinoline substitutions, hybrids, and electron-withdrawing groups against MTB H37Rv. Continued research is essential for developing potent, low-toxicity quinoline derivatives to combat tuberculosis.

Supplementation of Moringa oleifera leaf concentrate pellets on nutrient utilization, antioxidant status, and reproductive performance of prolific ewes during extreme summer months in semi-arid tropical conditions.

A feeding trial was conducted for a period of 60 days during extreme summer months to observe the effect of supplementation of Moringa oleifera leaves containing concentrate pellets on nutrient utilization, antioxidant status, and reproductive performance in Avishaan ewes reared under semi-arid condition. Forty adult non-pregnant cyclic ewes (2-3 years, 31.8 ± 0.81 kg body weight) were selected and randomly allocated into 2 groups of 20 animals each, viz., G-I (control) and G-II (treatment). The ewes were grazed on natural pasture for 8 h, offered ad libitum Cenchrus ciliaris hay after grazing and concentrate pellets @ 300 g/animal/day. The ewes in G-I were offered conventional concentrate pellets, whereas G-II ewes were offered concentrate pellets containing 15% Moringa leaves. The mean temperature humidity index during the period of study was 27.5 ± 0.3 and 34.6 ± 0.4 at 0700 h and 1400 h, respectively, indicating severe heat stress. Nutrient intake and utilization were comparable between the two groups. The antioxidant status was higher in G-II ewes as the values of catalase, superoxide dismutase, and total antioxidant capacity were higher (P < 0.05) in G-II ewes compared to G-I. The conception rate was higher (100%) in G-II ewes than G-I ewes (70%). Multiple birth percentage was 77.8% in G-II ewes, and it was comparable with the herd average of Avishaan (74.7%). However, ewes in G-I group exhibited a marked decline in multiple birth percentage (28.6%) than the normal herd average. Hence, it can be concluded that inclusion of Moringa oleifera leaves in feeding of prolific Avishaan ewes improved their antioxidant status resulting in optimum reproductive performance during stressful summer months.

Dietary n-3 PUFA augments pre-ovulatory follicle turnover and prolificacy in well-fed ewes.

The present study evaluated the effect of dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) on preovulatory follicle (POF) turnover, prolificacy, and endocrine and metabolic milieu in Malpura sheep. Fifty cyclic ewes with 3-3.5 body condition scores on a five-point scale were allocated equally to two groups (n = 25) following estrus synchronization and were supplemented with 0.6 mL/kg body weight of n-3 PUFA-rich fish oil (FO) or palm oil (PO) as control, for 60 d following an acclimatization period of 7 d. All ewes were mated with sexually active rams at the end of the supplementation period. On ultrasonographic ovarian scanning at the last fourth estrus, the mean number of POFs was 77.8% greater (P < 0.01) in FO ewes than in the PO ewes. The proportion of ewes with multiple ovulations two months after the beginning of supplementation was 56% in the FO group as compared to 8% in the PO group. The number of fetuses was 46% higher (P < 0.01) in the FO than in the PO ewes at d 45 of gestation. At lambing, the twinning percent in the FO ewes was three times greater than in the PO ewes (27.3 vs. 9.1%). Plasma cholesterol, estradiol, and insulin concentrations were lower (P < 0.01) in ewes fed with FO than those offered PO group at the end of the feeding period. It was concluded that the dietary supplementation of n-3 PUFA-rich FO in well-fed Malpura ewes improved the number of follicles and ovulation rate which led to an increased prolificacy, accompanied by a reduction of plasma cholesterols, estradiol, and insulin.

Evaluation of Therapeutic Potential of Selected Plant-Derived Homeopathic Medicines for their Action against Cervical Cancer.

BACKGROUND: Plant-derived homeopathic medicines (HMs) are cheap and commercially available but are mechanistically less explored entities than conventional medicines. PURPOSE: The aim of our study was to evaluate the impact of selected plant-derived HMs derived from Berberis aquifolium (BA), Berberis vulgaris (BV), Mentha piperita (MP), Curcuma longa (CL), Cinchona officinalis (CO), Thuja occidentalis (TO) and Hydrastis canadensis (HC) on cervical cancer (CaCx) cells in vitro. METHODS: We screened the mother tincture (MT) and 30C potencies of the above-mentioned HMs for anti-proliferative and cytotoxic activity on human papillomavirus (HPV)-negative (C33a) and HPV-positive CaCx cells (SiHa and HeLa) by MTT assay. Total phenolic content (TPC) and the free-radical scavenging activity of each HM was also determined using standard assays. Phytochemicals reportedly available in these HMs were examined for their potential inhibitory action on HPV16 E6 by in silico molecular docking. RESULTS: All tested MTs induced a differential dose-dependent cytotoxic response that varied with cell line. For C33a cells, the order of response was TO > CL > BA > BV > HC > MP > CO, whereas for SiHa and HeLa cells the order was HC > MP > TO > CO > BA > BV > CL and CL > BA > CO, respectively. 30C potencies of all HMs showed an inconsistent response. Further, anti-CaCx responses displayed by MTs did not follow the order of an HM's phenolic content or free radical scavenging activity. Analysis revealed anti-oxidant content of BA, BV and HC had the lowest contribution to their anti-CaCx activity. Using in silico modeling of molecular docking between the HPV16 E6 protein crystallographic structures (6SJA and 4XR8) and main phytochemical components of BV, BA, HC, CL and TO, their potential to inhibit the HPV16 E6 protein carcinogenic interactions was identified. CONCLUSION: The study has shown a comparative evaluation of the potential of several plant-derived MTs and HMs to affect CaCx cell line survival in vitro (through cytotoxicity and free radical scavenging) and their theoretical molecular targets in silico for the first time. Data demonstrated that MTs of BA and BV are likely to be the most potent HMs that strongly inhibited CaCx growth and have a strong anti-HPV phytochemical constitution.

Quantitative assessment of antioxidant potential of selected homeopathic preparations in clinical practice.

OBJECTIVES: Antioxidant property like radical scavenging is a primary target to elucidate the efficacy mechanism of a drug against diseases linked to oxidative stress such as cancer, metabolic disorders, rheumatoid arthritis, etc. In alternative therapies, homeopathy is one of the preferred choices by patients and clinicians due to its potential to cure chronic and complex illnesses. However, the efficacy of homeopathic preparations at high diluted potencies attracts rational criticism due to insufficient scientific knowledge supporting the mechanism of action. Therefore, an attempt was made to estimate the total phenolic content (TPC) and radical scavenging activity of clinically prescribed homeopathic drugs. METHODS: With gallic acid as a reference control, mother tinctures (MTs) and different potencies of Eucalyptus globulus (EG), Syzygium jambolanum (SJ), Ruta graveolens (RG), and Thuja occidentalis (TO) were used to perform Folin-Ciocalteu test, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. RESULTS: The results showed TPC of MTs equivalent to µg/mL of gallic acid viz; EG (4,872.5 ± 133.2), SJ (8,840.5 ± 14.8), RG (985.6 ± 39.1), and TO (341.5 ± 19.5) with significant ABTS and DPPH radical scavenging potential. Whereas 30C and 200C potencies of each homeopathic drug showed undetectable phenolic content and insignificant radical scavenging potential compared to vehicle control, i.e., alcohol 90% (2.0 ± 1.5). CONCLUSIONS: The reported efficacy of 30C and 200C potencies of homeopathic medicines against oxidative stress-related illnesses might be due to mechanisms other than radical scavenging. Furthermore, the assays studied can be helpful in drug standardization and quality control of MTs that are used as starting material in homeopathic preparations.

Current insights into epigenetics, noncoding RNA interactome and clinical pharmacokinetics of dietary polyphenols in cancer chemoprevention.

Several studies have reported the health-beneficial effects of dietary phytochemicals, namely polyphenols, to prevent various diseases, including cancer. Polyphenols, like (-)-epigallocatechin-3-gallate (EGCG) from green tea, curcumin from turmeric, and ellagic acid from pomegranate are known to act by modulating antioxidant, anti-inflammatory and apoptotic signal transduction pathways in the tumor milieu. The evolving literature underscores the role of epigenetic regulation of genes associated with cancer by these polyphenols, primarily via non-coding RNAs (ncRNAs), such as microRNAs (miRNA) and long noncoding RNA (lncRNA). However, there is little clarity on the exact role(s) played by these ncRNAs and their interactions with other ncRNAs, or with their protein targets, in response to modulation by these dietary polyphenols. Here, we review ncRNA interactions and functional networks of the complex ncRNA interactome with their targets in preclinical studies along with the role of epigenetics as well as key aspects of pharmacokinetics and phytochemistry of dietary polyphenols. We also summarize the current state of clinical trials with these dietary polyphenols. Taken together, this synthetic review provides insights into the molecular aspects underlying the anticancer chemopreventive effects of dietary polyphenols as well as summarizes data on novel biomarkers modulated by these polyphenols for preventive or therapeutic purposes in various types of cancer.

Illness wellness scale: novel grading system for performance status of patients under surgical care.

BACKGROUND: Grading the illness using clinical parameters is essential for the daily progress of inpatients. Existing systems do not incorporate these parameters holistically. The study was designed to internally validate the illness wellness scale, based upon clinical assessment of the patients requiring surgical care, for their risk stratification and uniformity of communication between health care providers. METHODS: Prospective observational study conducted at a tertiary care hospital. An expert panel devised the scale, and it was modified after feedback from 100 health care providers. A total of 210 patients (150 for internal validation and 60 for inter-observer variability) who required care under the department of surgical disciplines were enrolled. This included patients presenting to surgery OPD, admitted to COVID/non-COVID surgical wards and ICUs, aged ≥16 years. RESULTS: The response rate of the final illness wellness scale was 95% with 86% positive feedback and a mean of 1.7 on the Likert scale for ease of use (one being very easy and five being difficult). It showed excellent consistency and minimal inter-observer variability with the intra-class correlation coefficient (ICC) above 0.9. In the internal validation cohort (n = 150), univariate and multivariable analysis of factors affecting mortality revealed that categorical risk stratification, age ≥ 60 years, presence or absence of co-morbidities especially hypertension and chronic kidney disease significantly affect mortality. CONCLUSIONS: The Illness wellness scale is an effective tool for uniformly communicating between health care professionals and is also a strong predictor of risk stratification and mortality in patients requiring surgical care.

Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation.

Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.

Role of Vitamin A Supplementation in Prevention and Control of Coronavirus Disease-19: A Narrative Review.

Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 is a novel viral infectious disease, which broke out in the end of winter season 2019 in China and soon became a pandemic. Characteristically there was severe local and systemic immune-inflammatory response to the virus, damaging the respiratory system and other organ systems. The morbidity and mortality caused by the disease are producing tremendous impact on health. The understanding about pathogenesis and manifestations of the disease was obscure. To date, no classic treatment or preventive measure was available for COVID-19 other than symptomatic and supportive care or few drugs under trial. A possibility exists that maintaining vitamin A adequate levels can protect the affected respiratory mucosa, increase antimicrobial activity, produce better antibody response, and have antiinflammatory effects, thereby promoting repair and healing as well. It has been discussed in the review that by various mechanisms, immune regulation through vitamin A supplementation is beneficial to boost immunity in the current outbreak situation when the population is susceptible to the disease. There is a high possibility that vitamin A supplementation to cases as well as population at risk of COVID-19 has a key role in prevention and control. Hence, it is believed that along with other therapeutic and preventive measures, maintaining vitamin A sufficiency during and prior to the development of active disease may act as an adjuvant in population at risk and cases to prevent and control COVID-19.

Prevalence of anemia among toddlers (12-36 months) in urban area of district Rohtak, Haryana.

Background: Children are considered as an important asset for any country and their health as one of the important indicators of a healthy country. There are several factors affecting children's health and anemia is one of them. Globally around 1.62 billion people are affected by it, which corresponds to 24.8% of the population, with the highest prevalence of anemia (47.4%) among preschool-aged children. Aim: The present study was conducted to estimate the prevalence of anemia among toddlers (12-36 months) and to determine the associated factors. Materials and Methods: A cross-sectional study was carried out among toddlers (12-36 months) in the urban field practice area of Pt. B.D. Sharma PGIMS, Rohtak. A total of 170 toddlers were enrolled in the study and their mothers were interviewed using a semi-structured pretested questionnaire. Hb was estimated by Sahli's acid hematin method. The data were analyzed using SPSS software version 20. Results: In the present study, more than half (55.9%) participants were girls and 44.1% were boys. The overall prevalence of anemia was found to be 62.4%, with mild, moderate, and severe anemia being 41.8%, 17.7%, and 2.9%, respectively. The children with regular intake of iron supplementation were found to be 6.625 times likely to be nonanemic as compared to those with no supplementation. Conclusion: Every endeavor should be made to combat the anemia in children through multisectoral and multipronged approach such as nutritional education of mothers, growth monitoring, nutritional supplementation, etc.

The Perfect Imperfections in Electrocatalysts.

Modern day electrochemical devices find applications in a wide range of industrial sectors, from consumer electronics, renewable energy management to pollution control by electric vehicles and reduction of greenhouse gas. There has been a surge of diverse electrochemical systems which are to be scaled up from the lab-scale to industry sectors. To achieve the targets, the electrocatalysts are continuously upgraded to meet the required device efficiency at a low cost, increased lifetime and performance. An atomic scale understanding is however important for meeting the objectives. Transitioning from the bulk to the nanoscale regime of the electrocatalysts, the existence of defects and interfaces is almost inevitable, significantly impacting (augmenting) the material properties and the catalytic performance. The intrinsic defects alter the electronic structure of the nanostructured catalysts, thereby boosting the performance of metal-ion batteries, metal-air batteries, supercapacitors, fuel cells, water electrolyzers etc. This account presents our findings on the methods to introduce measured imperfections in the nanomaterials and the impact of these atomic-scale irregularities on the activity for three major reactions, oxygen evolution reaction (OER), oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER). Grain boundary (GB) modulation of the (ABO3 )n type perovskite oxide by noble metal doping is a propitious route to enhance the OER/ORR bifunctionality for zinc-air battery (ZAB). The perovskite oxides can be tuned by calcination at different temperatures to alter the oxygen vacancy, GB fraction and overall reactivity. The oxygen defects, unsaturated coordination environment and GBs can turn a relatively less active nanostructure into an efficient redox active catalyst by imbibing plenty of electrochemically active sites. Obviously, the crystalline GB interface is a prerequisite for effective electron flow, which is also applicable for the crystalline surface oxide shell on metal alloy core of the nanoparticles (NPs). The oxygen vacancy of two-dimensional (2D) perovskite oxide can be made reversible by the A-site termination of the nanosheets, facilitating the reversible entry and exit of a secondary phase during the redox processes. In several instances, the secondary phases have been observed to introduce the right proportion of structural defects and orbital occupancies for adsorption and desorption of reaction intermediates. Also, heterogeneous interfaces can be created by wrapping the perovskite oxide with negatively charged surface by layered double hydroxide (LDH) can promote the OER process. In another approach, ion intercalation at the 2D heterointerfaces steers the interlayer spacing that can influence the mass diffusion. Similar to anion vacancy, controlled formation of the cation vacancies can be achieved by exsolving the B-site cations of perovskite oxides to surface anchored catalytically active metal/alloy NPs. In case of the alloy electrocatalysts, incomplete solid solution by two or more mutually immiscible metals results in heterogeneous alloys having differently exposed facets with complementary functionalities. From the future perspective, new categories of defect structures including the 2D empty spaces or voids leading to undercoordinated sites, the multiple interfaces in heterogeneous alloys, antisite defects between anions and cations, and the defect induced inverse charge transfer should bring new dimensionalities to this riveting area of research.

Effect of limestone solubility on mineral digestibility and bone ash in nursery pigs fed diets containing graded level of inorganic phosphorus or increasing dose of a novel consensus bacterial 6-phytase variant.

The effect of a novel consensus bacterial 6-phytase variant (PhyG) on total tract digestibility (ATTD) of minerals and bone ash was evaluated in pigs fed diets containing medium- and high-solubility limestone (MSL and HSL, 69.6 and 91.7% solubility, respectively, at 5 min, pH 3.0) in a randomized complete block design. For each limestone, eight diets were formulated: an inorganic phosphate-free negative control (NC) based on wheat, corn, soybean-meal, canola-meal and rice-barn [0.18% standardized total tract digestible (STTD) P and 0.59% Ca]; the NC supplemented with 250, 500, 1,000, or 2,000 FTU/kg of PhyG, and; the NC with added monocalcium phosphate (MCP) and limestone to produce three positive controls (0.33, 0.27, and 0.21% STTD P, and 0.75, 0.70, and 0.64% Ca, respectively; PC1, PC2, PC3). In total, 128 pigs (12.8 ± 1.33 kg, 8 pigs/treatment, housed individually) were adapted for 16 d followed by 4 d of fecal collection. Femurs were collected from euthanized pigs on day 21. Data were analyzed by one-way ANOVA with means separation by Tukey's test, and by factorial analysis (2 x 4: 2 levels of limestone solubility, 4 STTD P levels, and 2 × 5: 2 levels of limestone solubility, 5 PhyG dose levels). Phytase dose-response was analyzed by curve fitting. A consistent negative effect of HSL on ATTD P and Ca was observed in control diets (P < 0.001). Across phytase-supplemented diets, HSL reduced (P < 0.05) ATTD Ca and P (% and g/kg) compared with MSL. Across limestones, increasing phytase dose level increased (P < 0.05) ATTD P exponentially. Limestone solubility had no effect on bone ash, but PhyG linearly increased (P < 0.05) bone ash; 500 FTU/kg or higher maintained bone ash (g/femur) equivalent to PC1. In conclusion, ATTD P and Ca were reduced by a high compared with a medium soluble limestone, but the novel phytase improved ATTD P and Ca independent of limestone solubility.

Microbial phytase is added to commercial pig diets to increase phosphorus (P) availability and reduce P excretion. It is known that an excess of calcium (Ca), mostly sourced from limestone, can affect phytase efficacy. However, less is known about the impact of limestone quality. This study investigated the effect of a medium- compared to a high-soluble limestone (MSL and HSL, respectively), in combination with increasing dose levels of a novel phytase (PhyG), on mineral digestibility and bone mineralization in young pigs. Without phytase, total tract digestibility of P was lower with HSL than MSL, indicating a negative effect of more soluble limestone on mineral digestibility. Increasing the phytase dose increased digestibility of P with either limestone, and reduced the negative effect of HSL at high dose. Bone mineralization was unaffected by limestone but markedly increased by phytase. At 1,000 FTU/kg, PhyG released an estimated 1.89 or 2.32 g/kg of digestible P from monocalcium phosphate in diets containing MSL and HSL, respectively based on bone ash content. The results demonstrate the efficacy of PhyG in young pig diets whilst indicating that limestone solubility can affect phytase efficacy.

Calcium phosphate adjuvanted nanoparticles of outer membrane proteins of Salmonella Typhi as a candidate for vaccine development against Typhoid fever.

Introduction. The conventional adjuvants used in vaccines have limitations like induction of an imbalanced Th1 and Th2 immune response. To overcome this limitation, novel adjuvants and newer forms of existing adjuvants like calcium phosphate nanoparticles are being tested.Hypothesis/Gap Statement. Calcium phosphate adjuvanted outer membrane proteins vaccine may work as an efficient, safe and cost effective vaccine against Salmonella Typhi.Aim. Our goals were to evaluate the potential of calcium phosphate nanoparticles as an adjuvant using outer membrane proteins (Omps) of Salmonella Typhi as antigens for immune response, with montanide (commercially available adjuvant) as control, and its toxicity in rats.Methodology. Calcium phosphate adjuvanted outer membrane proteins nanoparticles were synthesized and characterized. The efficacy of vaccine formulation in mice and toxicity assay were carried out in rats.Results. The calcium phosphate nanoparticles varying in size between 20-50 nm had entrapment efficiency of 41.5% and loading capacity of 54%. The calcium phosphate nanoparticle-Omps vaccine formulation (nanoparticle-Omps) induced a strong humoral immune response, which was significantly higher than the control group for the entire period of study. In the montanide-Omps group the initial very high immune response declined steeply and then remained steady. The immune response induced by nanoparticle-Omps did not change appreciably. The cell mediated immune response as measured by lymphocyte proliferation assay and delayed type hypersensitivity test showed a higher response (P<0.01) for the nanoparticles-Omps group as compared to montanide-Omps group. The bacterial clearance assay also showed higher clearance in the nanoparticles-Omps group as compared to montanide-Omps group (approx 1.4%). The toxicity analysis in rats showed no difference in the values of toxicity biomarkers and blood chemistry parameters, revealing vaccine formulation was non-toxic in rats.Conclusion. Calcium phosphate nanoparticles as adjuvant in vaccines is safe, have good encapsulation and loading capacity and induce a strong cell mediated, humoral and protective immune response.

Anti-migraine activity of freeze-dried latex obtained from Calotropis gigantea Linn.

Migraine which is characterized by a pulsating headache affected an estimated population of 12% worldwide. Herbal products like latex derived from Calotropis gigantea R. Br. (Asclepiadaceae) are a representative intervention to treat migraine traditionally. However, post-harvesting stability issues of latex affect its biological potential. Freeze-drying has been successfully employed for the encapsulation of herbal bioactive compounds resulting in stable dried preparations. Latex derived from Calotropis gigantea (C. gigantea) was microencapsulated using chitosan by freeze-drying (FDCG) method and compared with sun ray-dried latex (ADCG). Current investigation was aimed to improve the shelf life of latex by freeze-drying microencapsulation technique and evaluation of its anti-migraine potential. Dried latex powders (ADCG and FDCG) were evaluated in terms of phenolic content, coloring strength, first-order kinetic, color parameters (L*, a*, b*, C*, and E*), moisture, water activity, solubility, and hygroscopicity. Additionally, apomorphine-induced climbing behavior, L-5-HTP-induced syndrome, and MK-801-induced hyperactivity were used to evaluate the anti-migraine potential of powdered latex. FDCG showed good physicochemical properties due to its higher concentration of phenolic and flavonoid contents. Moreover, FDCG significantly reduced the apomorphine-induced climbing behavior, L-5-HTP-induced syndrome, and MK-801-induced hyperactivity in a dose-dependent manner through an interaction of dopaminergic and serotonergic receptors. In conclusion, the method developed for shelf life improvement of latex offered maximum protection over a period of 10 weeks with retaining its natural biological potential; thus, it can be effectively utilized in the treatment or management of migraine. Anti-migraine effect of Calotropis gigantea freeze-dried latex by inhibition of dopamine and serotonin receptors (D1 and D2: dopamine receptors; 5-HT: serotonin receptors); yellow color represents serotonergic, and blue color indicates dopaminergic neurons.

Transcriptome repository of North-Western Himalayan endangered medicinal herbs: a paramount approach illuminating molecular perspective of phytoactive molecules and secondary metabolism.

Medicinal plants of the North-Western Himalayan region are known for their unprecedented biodiversity and valuable secondary metabolites that are unique to this dynamic geo-climatic region. From ancient times these medicinal herbs have been used traditionally for their therapeutic potentials. But from the last 2 decades increasing pharmaceutical demand, illegal and unorganized trade of these medicinal plants have accelerated the rate of over-exploitation in a non-scientific manner. In addition, climate change and anthropogenic activities also affected their natural habitat and driving most of these endemic plant species to critically endangered that foresee peril of mass extinction from this eco-region. Hence there is an urgent need for developing alternative sustainable approaches and policies to utilize this natural bioresource ensuring simultaneous conservation. Hither, arise the advent of sequencing-based transcriptomic studies significantly contributes to better understand the background of important metabolic pathways and related genes/enzymes of high-value medicinal herbs, in the absence of genomic information. The use of comparative transcriptomics in conjunction with biochemical techniques in North-Western Himalayan medicinal plants has resulted in significant advances in the identification of the molecular players involved in the production of secondary metabolic pathways over the last decade. This information could be used to further engineer metabolic pathways and breeding programs, ultimately leading to the development of in vitro systems dedicated to the production of pharmaceutically important secondary metabolites at the industrial level. Collectively, successful adoption of these approaches can certainly ensure the sustainable utilization of Himalayan bioresource by reducing the pressure on the wild population of these critically endangered medicinal herbs. This review provides novel insight as a transcriptome-based bioresource repository for the understanding of important secondary metabolic pathways genes/enzymes and metabolism of endangered high-value North-Western Himalayan medicinal herbs, so that researchers across the globe can effectively utilize this information for devising effective strategies for the production of pharmaceutically important compounds and their scale-up for sustainable usage and take a step forward in omics-based conservation genetics.

Digitalization to achieve sustainable development goals: Steps towards a Smart Green Planet.

Digitalization provides access to an integrated network of unexploited big data with potential benefits for society and the environment. The development of smart systems connected to the internet of things can generate unique opportunities to strategically address challenges associated with the United Nations Sustainable Development Goals (SDGs) to ensure an equitable, environmentally sustainable, and healthy society. This perspective describes the opportunities that digitalization can provide towards building the sustainable society of the future. Smart technologies are envisioned as game-changing tools, whereby their integration will benefit the three essential elements of the food-water-energy nexus: (i) sustainable food production; (ii) access to clean and safe potable water; and (iii) green energy generation and usage. It then discusses the benefits of digitalization to catalyze the transition towards sustainable manufacturing practices and enhance citizens' health wellbeing by providing digital access to care, particularly for the underserved communities. Finally, the perspective englobes digitalization benefits by providing a holistic view on how it can contribute to address the serious challenges of endangered planet biodiversity and climate change.

Genome-wide identification and expression profiling of basic leucine zipper transcription factors following abiotic stresses in potato (Solanum tuberosum L.).

Potato (Solanum tuberosum L.) is an important food crop that is grown and consumed worldwide. The growth and productivity of this crop are severely affected by various abiotic stresses. Basic leucine zipper (bZIP) transcription factors (TFs) in plants are well known for their function during growth and development. However, systematic and in-depth identification and functional characterization of the bZIP gene family of potato is lacking. In the current study, we identified a total of 90 bZIPs (StbZIP) distributed on 12 linkage groups of potato. Based on the previous functional annotation and classification of bZIPs in Arabidopsis, wheat, and rice, a phylogenetic tree of potato bZIPs was constructed and genes were categorized into various functional groups (A to I, S, and U) as previously annotated in Arabidopsis thaliana. Analyses of the transcript sequence (RNA-seq) data led to identifying a total of 18 candidate StbZIPs [four in roots, eight in the tuber, six in mesocarp and endocarp] that were expressed in a tissue-specific manner. Differential expression analysis under the various abiotic conditions (salt, mannitol, water, and heat stress) and treatment with phytohormones (ABA, GA, IAA, and BAP) led to the identification of forty-two [thirteen under salt stress, two under mannitol stress, ten under water stress, and eighteen under heat stress], and eleven [eight and three StbZIPs upon treatment with ABA, and IAA, respectively] candidate StbZIPs, respectively. Using sequence information of candidate StbZIPs, a total of 22 SSR markers were also identified in this study. In conclusion, the genome-wide identification analysis coupled with RNA-Seq expression data led to identifying candidate StbZIPs, which are dysregulated, and may play a pivotal role under various abiotic stress conditions. This study will pave the way for future functional studies using forward and reverse genetics to improve abiotic stress tolerance in potato.

Ligand decorated biodegradable nanomedicine in the treatment of cancer.

Cancer is one of the major global health problems, responsible for the second-highest number of deaths. The genetic and epigenetic changes in the oncogenes or tumor suppressor genes alter the regulatory pathways leading to its onset and progression. Conventional methods are used in appropriate combinations for the treatment. Surgery effectively treats localized tumors; however, it fails to treat metastatic tumors, leading to a spread in other organs, causing a high recurrence rate and death. Among the different strategies, the nanocarriers-based approach is highly sought for, but its nonspecific delivery can cause a profound side effect on healthy cells. Targeted nanomedicine has the advantage of targeting cancer cells specifically by interacting with the receptors overexpressed on their surface, overcoming its non-specificity to target healthy cells. Nanocarriers prepared from biodegradable and biocompatible materials are decorated with different ligands by encapsulating therapeutic or diagnostic agents or both to target cancer cells overexpressing the receptors. Scientists are now utilizing a theranostic approach to simultaneously evaluate nanocarrier bio-distribution and its effect on the treatment regime. Herein, we have summarized the recent 5-year efforts in the development of the ligands decorated biodegradable nanocarriers, as a targeted nanomedicine approach, which has been highly promising in the treatment of cancer.

Unfolding Nrf2 in diabetes mellitus.

In spite of much awareness, diabetes mellitus continues to remain one of major reasons for mortality and morbidity rate all over the globe. Free radicals cause oxidative stress which is responsible for causing diabetes. The recent advancements in elucidation of ARE/keap1/Nrf2 pathway can help in better understanding of diabetes mellitus. Various clinical trials and animal studies have shown the promising effect of Nrf2 pathway in reversing diabetes by counteracting with the oxidative stress produced. The gene is known to dissociate from Keap1 on coming in contact with such stresses to show preventive and prognosis effect. The Nrf2 gene has been marked as a molecular player in dealing with wide intracellular as well as extracellular cellular interactions in different diseases. The regulation of this gene gives some transcription factor that contain antioxidant response elements (ARE) in their promoter region and thus are responsible for encoding certain proteins involved in regulation of metabolic and detoxifying enzymes.