A Metamaterial-like Structure Design Using Non-uniformly Distributed Dielectric and Conducting Strips to Boost the RF Field Distribution in 7 T MRI.

Metamaterial-based designs in ultra-high field (≥7 T) MRI have the promise of increasing the local magnetic resonance imaging (MRI) signal and potentially even the global efficiency of both the radiofrequency (RF) transmit and receive resonators. A recently proposed metamaterial-like structure-comprised of a high-permittivity dielectric material and a set of evenly distributed copper strips-indeed resulted in a local increase in RF transmission. Here, we demonstrate that non-uniform designs of this metamaterial-like structure can be used to boost the ultimate RF field distribution. A non-uniform dielectric distribution can yield longer electric dipoles, thus extending the RF transmit field coverage. A non-uniform distribution of conducting strips enables the tailoring of the local electric field hot spots, where a concave distribution resulted in lower power deposition. Simulations of the brain and calf regions using our new metamaterial-like design, which combines non-uniform distributions of both the dielectric and conducting strips, revealed a 1.4-fold increase in the RF field coverage compared to the uniform distribution, and a 1.5-2-fold increase in the transmit efficiency compared to the standard surface-coil.

Neolamarckia cadamba (Roxb.) Bosser (Rubiaceae) extracts: promising prospects for anticancer and antibacterial potential through in vitro and in silico studies.

Neolamarckia cadamba is an Indian traditional medicinal plant having various therapeutic potentials. In the present study, we did solvent-based extraction of Neolamarckia cadamba leaves. The extracted samples were screened against liver cancer cell line (HepG2) and bacteria (Escherichia coli). MTT cytotoxic assay was performed for in vitro analysis of extracted samples against the HepG2 cell lines and the normal human prostate PNT2 cell line. Chloroform extract of Neolamarckia cadamba leaves showed better activity with IC50 value 69 µg/ml. DH5α strain of Escherichia coli (E. coli) was cultured in Luria Bertani (LB) broth media and minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were calculated. Solvent extract chloroform showed better activity in MTT analysis and antibacterial screening and it was taken for characterization of phytocomposition by Fourier transform infrared (FTIR) and gas chromatography mass spectrometry (GC-MS). The identified phytoconstituents were docked with potential targets of liver cancer and E. coli. The phytochemical 1-(5-Hydroxy-6-hydroxymethyl-tetrahydropyran-2-yl)-5-methyl-1H-pyrimidine-2,4-dione shows highest docking score against the targets PDGFRA (PDB ID: 6JOL) and Beta-ketoacyl synthase 1(PDB ID: 1FJ4) and their stability was further confirmed by molecular dynamics simulation studies.

Withaniasomnifera phytochemicals possess SARS-CoV-2 RdRp and human TMPRSS2 protein binding potential.

Abstract: Coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has infected approximately 26 million people and caused more than 6 million deaths globally. Spike (S)-protein on the outer surface of the virus uses human trans-membrane serine protease-2 (TMPRSS2) to gain entry into the cell. Recent reports indicate that human dipeptidyl peptidase-4 inhibitors (DPP4 or CD26) could also be utilized to check the S-protein mediated viral entry into COVID-19 patients. RNA dependent RNA polymerase (RdRp) is another key virulence protein of SARS-CoV-2 life cycle. The study aimed to identify the potential anti-SARS-CoV-2 inhibitors present in Withania somnifera (Solanaceae) using computer aided drug discovery approach. Molecular docking results showed that flavone glycoside, sugar alcohol, and flavonoid present in W. somnifera showed - 11.69, - 11.61, - 10.1, - 7.71 kcal/mole binding potential against S-protein, CD26, RdRp, and TMPRSS2 proteins. The major standard inhibitors of the targeted proteins (Sitagliptin, VE607, Camostat mesylate, and Remdesivir) showed the - 7.181, - 6.6, - 5.146, and - 7.56 kcal/mole binding potential. Furthermore, the lead phytochemicals and standard inhibitors bound and non-bound RdRp and TMPRSS2 proteins were subjected to molecular dynamics (MD) simulation to study the complex stability and change in protein conformation. The result showed energetically favorable and stable complex formation in terms of RMSD, RMSF, SASA, Rg, and hydrogen bond formation. Drug likeness and physiochemical properties of the test compounds exhibited satisfactory results. Taken together, the present study suggests the presence of potential anti-SARS-CoV-2 phytochemicals in W. somnifera that requires further validation in in vitro and in vivo studies. Supplementary information: The online version contains supplementary material available at 10.1007/s42535-022-00404-4.

Relationship between biochemical parameters of mineral bone disease and static bone histomorphometry in chronic kidney disease patients on hemodialysis: An Indian cross-section study.

AIM: We estimated the relationship between routine biochemical laboratory parameters with static bone histomorphometric parameters and their high and low bone turnover capacity predictability in hemodialysis patients. METHOD: It was a single-center cross-sectional study, included 28 hemodialysis patients. The routine biochemical parameters measured including calcium, phosphorous, alkaline phosphatase, intact PTH, and 25-hydroxycholecalciferol. The histomorphometric parameters assessed were osteoblasts perimeter, osteoclast perimeter, eroded perimeter, osteoid perimeter, bone fibrosis and bone volume. RESULT: Total 28 hemodialysis patients underwent bone biopsy. Seventy percent were male, with a mean age was 33.07±10.42 yrs; serum alkaline phosphatase was 219.10±311.3IU/ml; vitamin D was 18.18±9.56ng/ml, and intact PTH was 650.7±466.0pg/ml. Intact PTH had a significant positive association with osteoblast, osteoclast, eroded surface, and osteoid perimeter. Serum alkaline phosphatase had a significant relationship with bone fibrosis (r=0.525, p-value=0.004). Intact PTH was significantly higher in females than males (1078.75±533.04 vs. 479.6±309.83; p-value=0.004). The osteoid surface was significantly high in females compared to males (p=0.038). Age had a significant impact on osteoblast and eroded surface (p=0.008 and p=0.031, respectively). Intact PTH is a reliable biomarkers for bone turnover compare to ALP (p<0.001 and p=0.554, respectively). CONCLUSION: Intact PTH strongly associated with bone formation, bone resorption parameters. Gender and age had significant impact on static histomorphometric parameters in our study.

Role of lupeol in chemosensitizing therapy-resistant prostate cancer cells by targeting MYC, ß-catenin and c-FLIP: in silico and in vitro studies.

Prostate cancer (CaP) is one of the most frequent malignancies amongst men. Enzalutamide is the second-generation potent androgen receptor (AR) antagonist used against metastatic and non-metastatic CaP. Unfortunately, the development of chemoresistance in cancer cells reduces the effectiveness of Enzalutamide. Lupeol is a pentacyclic triterpene found in different fruits, vegetables, and medicinal plants and possesses anti-inflammatory and anti-cancer properties. Here, we report in silico and in vitro studies of Lupeol and Enzalutamide against the ß-CATENIN, c-FLIPL, and c-MYC, which play a significant role in chemoresistance. We observed that Lupeol significantly inhibits the cell growth of chemoresistant Du145 cells and cancer stem cells (CSCs) either alone or in combination with Enzalutamide. Lupeol and Enzalutamide were also found to dock with ß-CATENIN, c-FLIPL, and c-MYC. The following MD simulation data showed both compounds exerting structural changes in these proteins. Finally, they significantly inhibit the transcriptional activity of all these genes, as observed by luciferase assay. Thus, we infer that Lupeol chemosensitizes the CaP cells for Enzalutamide-resistant CaP cells.

Role of SERCA Pump in Muscle Thermogenesis and Metabolism.

In muscle cells, the sarcoplasmic reticulum (SR) not only acts as a Ca2+ store, but also regulates the contractile characteristics of the muscle. Ca2+ release from the SR is the primary mechanism for activating muscle contraction and reuptake of Ca2+ by the sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump causes muscle relaxation. The SERCA pump isoforms are encoded by three genes, SERCA 1, 2, and 3, which are differentially expressed in muscle and determine SR Ca2+ dynamics by affecting the rate and amount of Ca2+ uptake, thereby affecting SR store and release of Ca2+ in muscle. In muscle, small molecular weight proteins, including Phospholamban (PLB) and Sarcolipin (SLN), also regulate the SERCA pump. Regulation of the SERCA pump by PLB or SLN affects cytosolic Ca2+ dynamics and changes in cytosolic Ca2+ not only affect contractile function, but also mitochondrial ATP production. Recent studies have shown that alterations in cytosolic Ca2+ affects Ca2+ entry into mitochondria and ATP production; thus, Ca2+ serves as an integrating signal between muscle contraction-dependent energy demand and mitochondrial energy production. In addition, changes in cytosolic Ca2+ can affect Ca2+ signaling pathways modulating gene expression and muscle growth. An emerging area of research shows that SR Ca2+ cycling is also a player in muscle-based nonshivering thermogenesis. Recent data shows that SERCA uncoupling by SLN leads to increased ATP hydrolysis and heat production. Our studies, using genetically altered mouse models of SLN, show that SLN/SERCA interaction plays an important role in muscle thermogenesis and metabolism, which will be discussed here, in great length. © 2017 American Physiological Society. Compr Physiol 7:879-890, 2017.

Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review.

Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.

Preliminary Screening of a Classical Ayurvedic Formulation for Anticonvulsant Activity.

BACKGROUND: Epilepsy is a serious and complex central nervous system disorder associated with recurrent episodes of convulsive seizures due to the imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmitters level in the brain. The available treatments are neither competent to control the seizures nor prevent progress of disease. Since ages, Herbal medicines have remained important sources of medicines in many parts of world which is evidenced through their uses in traditional systems of medicine i.e. Ayurveda, Siddha, Unani, Homeopathy and Chinese etc. AIM: A polyherbal formulation (containing Terminalia chebula Retz., Asparagus racemosus Willd., Embelia ribes Burm. F, Acorus calamus L., Tinospora cordifolia (Willd.) Miers, Convolvulus pluricaulis Choisy, Saussurea lappa C.B.Clarke, Achyranthes aspera L.) is mentioned in Ayurvedic classics Bhaisajya Ratnavali. The aim of the study was to evaluate the anticonvulsant activity of the formulation in Maximum electroshock and Pentylenetetrazole induced convulsions in rats. MATERIALS AND METHODS: In the present study, a polyherbal formulation was developed as directed by classical text and evaluated for the anticonvulsant activity using Maximal Electroshock Shock (MES) and Pentylenetetrazole (PTZ) induced convulsions in rats. Statistical comparison was done by one way ANOVA followed by the Tukey's multiple comparison test. RESULTS: The obtained results showed that the PHF had a protective role on epilepsy. Treatment with PHF significantly improves antioxidant enzymes activities of superoxide dismutase (SOD) and glutathione (GSH) levels significantly as compared to controls. PHF also significantly decreased malonaldialdehyde (MDA) levels in the brain. Moreover, it also attenuated the PTZ-induced increase in the activity of GABA-T in the rat brain. CONCLUSION: These findings suggest that PHF might have possible efficacy in the treatment of epilepsy.

Sarcolipin is a novel regulator of muscle metabolism and obesity.

Obesity is increasing at an alarming rate, both in adults and adolescents, across the globe due to increased consumption of caloric rich diet. Obesity and its associated complications appear to be major contributing factors not only to diabetes/heart disease but also to cancer, and neurological diseases causing a huge burden on the health care system. To date, there are no effective treatments to reduce weight gain, other than caloric restriction and exercise which are often difficult to enforce. There are very few drugs available for treating obesity and those that are available only reduce obesity by ∼ 10%. Identifying mechanisms to increase energy expenditure, on top of the increase elicited by exercise, would be more beneficial to control weight gain. The purpose of this review is to highlight the role of sarcolipin (SLN), a regulator of SERCA pump, in muscle thermogenesis and metabolism. We will further discuss if enhancing SLN activity could be an effective mechanism to increase energy expenditure and control weight gain. We will also discuss the merits of adaptive thermogenesis in muscle and brown fat as potential mechanisms to increase energy expenditure during caloric overload. That said, there is still a great need for further research into the mechanism of diet induced thermogenesis and its relevance to overall metabolism and obesity.

Ethnomedicinal review of Usnakantaka (Echinops echinatus Roxb.).

Echinops echinatus Roxb. (E. echinatus), commonly known as "Usnakantaka," is a xerophytic herbaceous plant traditionally used as a stimulant to treat use the term Sexual debility in Indian traditional systems of medicine. The roots, leaves, fruit, and bark are extensively used in folk medicine as well as in Ayurveda. Also, the plant shows a wide range of pharmacological activities such as antifungal, analgesic, diuretic, reproductive, hepatoprotective, antioxidant, anti-inflammatory, wound-healing, antipyretic, and antibacterial properties. Among the several active constituents, apigenin, apigenin-7-O-glucoside, echinaticin, 5,7-dihydroxy-8,4'-dimethoxy-flavanone-5-O-α-L-rhamnopyranosyl-7-O - ß-D-arabinopyranosyl-(1→4)-O-ß-D-glucopyranoside are the most important in terms of reported pharmacological activities. The current review focuses on the updated information from various scientific studies and reports available in the context of the phytoconstituents and pharmacology of this plant. This review also provides adequate information about the use of this plant in an Indian system of medicine, Ayurveda.

Sodhana: An Ayurvedic process for detoxification and modification of therapeutic activities of poisonous medicinal plants.

Ayurveda involves the use of drugs obtained from plants, animals, and mineral origin. All the three sources of drugs can be divided under poisonous and nonpoisonous category. There are various crude drugs, which generally possess unwanted impurities and toxic substances, which can lead to harmful health problems. Many authors have reported that not all medicinal plants are safe to use since they can bear many toxic and harmful phytoconstituents in them. Sodhana (detoxification/purification) is the process, which involves the conversion of any poisonous drug into beneficial, nonpoisonous/nontoxic ones. Vatsanabha (Aconitum species), Semecarpus anacardium, Strychnos nux-vomica, Acorus calamus, Abrus precatorius etc., are some of the interesting examples of toxic plants, which are still used in the Indian system of medicine. Aconite, bhilawanols, strychnine, ß-asarone, abrin are some of the toxic components present in these plants and are relatively toxic in nature. Sodhana process involves the purification as well as reduction in the levels of toxic principles which sometimes results in an enhanced therapeutic efficacy. The present review is designed to extensively discuss and understand the scientific basis of the alternative use of toxic plants as a medicine after their purification process.

Clinical Efficacy of Moringa oleifera Lam. Stems Bark in Urinary Tract Infections.

Objective. Urinary tract infections (UTI) are the most common problem in clinical practice. Usually they are asymptomatic and are commonly present with distressing symptoms like pain and burning sensation on urination. Antibiotics are widely used to treat UTIs; however, they have their own limitations like resistance, reinfection, and relapses. The purpose of the current study was to evaluate the value of Moringa oleifera Lam. stem bark as a potential medicine for UTIs. Study Design. 30 patients with UTI were randomly divided into two groups with 15 patients in each group. Shigru bark was given to patients of the first group (trial group) and modern medicines were prescribed to the other group of patients. At least three follow-ups are taken in both groups at the end of every week of treatment. Results. After treatment 66.67 % were cured, 13.33 % improved, 13.33% patients have no change, and 6.67% relapsed in trial group and in control group 46.67% were cured, 26.66% improved, 6.67% patients have no change, and 20% relapsed. Interpretation and Conclusion. The trial drug is significant in the management of UTI. This study needs to be done on a large scale and for a long time.

Antidyslipidaemic activity of Glycyrrhiza glabra in high fructose diet induced dsyslipidaemic Syrian golden hamsters.

The root of Glycyrrhiza glabra is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. Glycyrrhizinic acid, a major component of licorice, has antiulcer effect by raising the local concentration of prostaglandins that promote mucous secretion and cell proliferation in the stomach. Glycyrrhizin shows hepatoprotective effect by preventing changes in cell membrane permeability, inhibiting phospholipase A(2) (PLA(2)) and increasing survival rate of hepatocytes. Glabridin has effect in melanogenesis and inflammation by inhibiting the tyrosinase activity of melanocytes. α-glycyhrritinic acid exhibits anti-inflammatory activity by inhibiting glucocorticoid metabolism. In present study ethanolic (95%) extract of root of Glycyrrhiza glabra and its fractions were investigated for its antidyslipidaemic activity on HFD induced dyslipidaemic hamsters. Ethanolic extract and its ethyl acetate soluble, water soluble and hexane soluble fractions decreased serum level of total cholesterol by 25.9, 38.0, 39.0 and 26.3%, respectively. On the other hand ethanolic extract, ethyl acetate soluble, water soluble and hexane soluble fraction increased the serum HDL-cholesterol level by 14.8, 34.3, 27.3 and 17.2%, respectively. Ethanolic extract, ethyl acetate fraction, aqueous fraction and hexane fraction decreased triglyceride level by 31.3, 37.2, 41.2 and 28.9%, respectively. The reduction in LDL-cholesterol level by ethanolic extract, ethyl acetate soluble fraction and water soluble fraction were 43.9, 31.0, 33.4 and 24.6%, respectively.