Antimicrobial potential of phytocompounds of Acorus calamus: in silico approach.

Medicinal plants are used from prehistoric time to cure various life-threatening bacterial diseases. Acorus calamus is an important medicinal plant widely used to cure gastrointestinal, respiratory, kidney and liver disorders. The objective of the current research was to investigate the interaction of major phytoconstituents of Acorus calamus with bacterial (6VJE) and fungal (1EA1) protein targets. Protein-ligand interactions were estimated using the AutoDock software, drug likeness was predicted by using the molinspiration server and toxicity was predicted with the swissADME and protox II servers. MD simulation of phytocompounds with the best profiles was done on the GROMACS software for 100 ns. Molecular docking results showed among all the selected major phytoconstituents, that ß-cadinene showed best binding interaction in complex with bacterial (6VJE) and fungal (1EA1) protein targets with binding energy -7.66 ± 0.1 and -7.73 ± 0.15 kcal mol-1, respectively. Drug likeness and toxicity predictions showed that ß-cadinene follows all rules of drug likeness and toxicity. MD simulation study revealed that ß-cadinene fit in binding pocket of bacterial and fungal targets and found to be stable throughout the duration of the simulation. Based on the observations from this in-silico study it is being proposed that ß-cadinene, a major phytocompound of Acorus calamus, can be considered for the treatment of bacterial and fungal infections since the study shows that it might be one of the compounds that contributes majorly to the plant's biological activity. This study needs in vitro and in vivo validation.Communicated by Ramaswamy H. Sarma.

A Choice-Based Design Approach to Influence Beneficial Use of a Green Space by Family Caregivers at a Tertiary Care Hospital in India.

OBJECTIVES, PURPOSES, AND AIMS: Principles of behavioral economics are now being used across fields in changing human behavior toward perceived benefit. We studied the effectiveness of simple, cost-effective design cues based on these principles, in encouraging use of a neglected outdoor space in a hospital. BACKGROUND: Benefits of access to nature and green spaces are established in healthcare; however, we found utilization of an outdoor space to be suboptimal. Presenting choices in different ways is known to influence user choice. METHODS: We designed four design interventions based to nudge relative-caregivers waiting outside the operation theater toward utilizing an adjoining outdoor balcony. These included making the terrace prominent, reducing indoor sensory stimulation, adding stereotypical elements, and improving usability. We measured usage via video camera data and satisfaction using questionnaires. RESULTS: The number of users and average time per person spent on the balcony increased over the consecutive intervention periods as compared to baseline (trend p < .01 for both), mainly driven by the addition of stereotypical elements. There were no adverse events in the balcony. There was no difference in the satisfaction related outcomes on questionnaire; a larger percentage of positive comments tended to be related to the balcony in the final intervention. CONCLUSIONS: Cost-effective design cues nudged patient-caregivers toward spending more time with nature, thus changing behavior toward that with perceived benefits.

Synbiotic Effects of Fermented Rice on Human Health and Wellness: A Natural Beverage That Boosts Immunity.

Fermented foods have been an important component of the human diet from the time immemorial. It contains a high amount of probiotics that have been associated to a wide range of health benefits, including improved digestion and immunity. This review focuses on the indigenously prepared prebiotic- and probiotic-containing functional fermented rice (named Xaj-pani) by the Ahom Community from Assam, in Northeast India, including all the beneficial and potential effects on human health. Literature was searched from scientific databases such as PubMed, ScienceDirect and Google Scholar. Glutinous rice (commonly known as bora rice of sali variety) is primarily employed to prepare beverages that are recovered through the filtration process. The beer is normally consumed during religious rites, festivals and ritual practices, as well as being used as a refreshing healthy drink. Traditionally, it is prepared by incorporating a variety of medicinal herbs into their starter culture (Xaj-pitha) inoculum which is rich in yeasts, molds and lactic acid bacteria (LAB) and then incorporated in alcoholic beverage fermentation. The Ahom communities routinely consume this traditionally prepared alcoholic drink with no understanding of its quality and shelf life. Additionally, a finally produced dried cake, known as vekur pitha act as a source of Saccharomyces cerevisiae and can be stored for future use. Despite the rampant use in this community, the relationship between Xaj-pani's consumption, immunological response, infectious and inflammatory processes remains unknown in the presence of factors unrelated or indirectly connected to immune function. Overall, this review provides the guidelines to promote the development of prebiotic- and probiotic-containing functional fermented rice that could significantly have an impact on the health of the consumers.

Antibacterial Potential of Bacopa monnieri (L.) Wettst. and Its Bioactive Molecules against Uropathogens-An In Silico Study to Identify Potential Lead Molecule(s) for the Development of New Drugs to Treat Urinary Tract Infections.

Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. Bacopa monnieri is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of B. monnieri leaves and its bioactive molecules against UTIs that are caused by Klebsiella pneumoniae and Proteus mirabilis. This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of B. monnieri leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the Klebsiella pneumoniae fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of B. monnieri revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against K. pneumoniae with the use of increasing concentrations. In the case of P. mirabilis activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. Carbohydrates, flavonoids, saponin, phenolic, and terpenoid were common phytoconstituents identified in B. monnieri extracts. Oroxindin showed the best interactions with the binding energies with 5WEW and 6Y4F, -7.5 kcal/mol and -7.4 kcal/mol, respectively. Oroxindin, a bioactive molecule, followed Lipinski's rule of five and exhibited stability in the MD simulation. The overall results suggest that Oroxindin from B. monnieri can be a potent inhibitor for the effective killing of K. pneumoniae and P. mirabilis. Additionally, its safety has been established, indicating its potential for future drug discovery and development in the treatment for UTIs.

A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin.

Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constituent of C. longa, is well known for its therapeutic potential in numerous disorders. However, there is a lack of literature on the therapeutic potential of C. longa in contrast to curcumin. Hence, the present review aimed to provide in-depth information by highlighting knowledge gaps in traditional and scientific evidence about C. longa in relation to curcumin. The relationship to one another in terms of biological action includes their antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, cardioprotective, immunomodulatory, antifertility, antimicrobial, antiallergic, antidermatophytic, and antidepressant properties. Furthermore, in-depth discussion of C. longa on its taxonomic categorization, traditional uses, botanical description, phytochemical ingredients, pharmacology, toxicity, and safety aspects in relation to its major compound curcumin is needed to explore the trends and perspectives for future research. Considering all of the promising evidence to date, there is still a lack of supportive evidence especially from clinical trials on the adjunct use of C. longa and curcumin. This prompts further preclinical and clinical investigations on curcumin.

Role of Dexamethasone and Methylprednisolone Corticosteroids in Coronavirus Disease 2019 Hospitalized Patients: A Review.

The WHO announced coronavirus disease 2019 (COVID-19) as a pandemic disease globally on March 11, 2020, after it emerged in China. The emergence of COVID-19 has lasted over a year, and despite promising vaccine reports that have been produced, we still have a long way to go until such remedies are accessible to everyone. The immunomodulatory strategy has been kept at the top priority for the research agenda for COVID-19. Corticosteroids have been used to modulate the immune response in a wide range of diseases for the last 70 years. These drugs have been shown to avoid and reduce inflammation in tissues and the bloodstream through non-genomic and genomic effects. Now, the use of corticosteroids increased the chance of survival and relief by combating the viral strong inflammatory impacts and has moved to the forefront in the management of patients seeking supplemental oxygen. The goal of this review is to illuminate dexamethasone and methylprednisolone, i.e., in terms of their chemical and physical properties, role in COVID-19 patients suffering from pneumonia, the proposed mode of action in COVID-19, pharmacokinetics, pharmacodynamics, clinical outcomes in immunocompromised populations with COVID-19, interaction with other drugs, and contradiction to explore the trends and perspectives for future research. Literature was searched from scientific databases such as Science Direct, Wiley, Springer, PubMed, and books for the preparation of this review. The RECOVERY trial, a massive, multidisciplinary, randomized, and open-label trial, is mainly accountable for recommendations over the usage of corticosteroids in COVID-19 patients. The corticosteroids such as dexamethasone and methylprednisolone in the form of medication have anti-inflammatory, analgesic, and anti-allergic characteristics, including the ability to inhibit the immune system. These drugs are also recommended for treating symptoms of multiple ailments such as rheumatic and autoimmune diseases, leukemia, multiple myeloma, and Hodgkin's and non-Hodgkin's lymphoma along with other drugs. Toxicology studies proved them safe usually at low dosage via oral or other routes.

Phytoconstituents of traditional Himalayan Herbs as potential inhibitors of Human Papillomavirus (HPV-18) for cervical cancer treatment: An In silico Approach.

Human papillomavirus (HPV) induced cervical cancer is becoming a major cause of mortality in women. The present research aimed to identify the natural inhibitors of HPV-18 E1 protein (1R9W) from Himalayan herbs with lesser toxicity and higher potency. In this study, one hundred nineteen phytoconstituents of twenty important traditional medicinal plants of Northwest Himalayas were selected for molecular docking with the target protein 1R9W of HPV-18 E1 Molecular docking was performed by AutoDock vina software. ADME/T screening of the bioactive phytoconstituents was done by SwissADME, admetSAR, and Protox II. A couple of best protein-ligand complexes were selected for 100 ns MD simulation. Molecular docking results revealed that among all the selected phytoconstituents only thirty-five phytoconstituents showed the binding affinity similar or more than the standard anti-cancer drugs viz. imiquimod (-6.1 kJ/mol) and podofilox (-6.9 kJ/mol). Among all the selected thirty-five phytoconstituents, eriodictyol-7-glucuronide, stigmasterol, clicoemodin and thalirugidine showed the best interactions with a docking score of -9.1, -8.7, -8.4, and -8.4 kJ/mol. Based on the ADME screening, only two phytoconstituents namely stigmasterol and clicoemodin selected as the best inhibitor of HPV protein. MD simulation study also revealed that stigmasterol and clicoemodin were stable inside the binding pocket of 1R9W, Stigmasterol and clicoemodin can be used as a potential investigational drug to cure HPV infections.

Role of medicinal plants from North Western Himalayas as an efflux pump inhibitor against MDR AcrAB-TolC Salmonella enterica serovar typhimurium: In vitro and In silico studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Zingiber officinale Roscoe has been utilized traditionally to cure various diseases like cold, cough, diarrhoea, nausea, asthma, vomiting, toothache, stomach upset, respiratory disorders, joint pain, and throat infection. It is also consumed as spices and ginger tea. AIM OF THE STUDY: The current study was aimed to identify the phytocompounds of traditional medicinal plants of North-Western Himalaya that could inhibit the AcrAB-TolC efflux pump activity of Salmonella typhimurium and become sensitive to antibiotic killing at reduced dosage. MATERIAL AND METHODS: Medicinal plant extracts were prepared using methanol, aqueous, and ethyl acetate and tested for efflux pump inhibitory activity of Salmonella typhimurium NKS70, NKS174, and NKS773 strains using Ethidium Bromide (EtBr)-agar cartwheel assay. Synergism was assessed by the agar well diffusion method and EPI activity by berberine uptake and EtBr efflux inhibition assays. Microdilution method and checkerboard assays were done to determine the minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) respectively for a bioactive compound. To validate the phytocompound and efflux pump interaction, molecular docking with 6IE8 (RamA) and 6IE9 (RamR) targets was done using autoDock vina software. Toxicity prediction and drug-likeness were predicted by using ProTox-II and Molinspiration respectively. RESULTS: Methanolic and ethyl acetate extracts of P. integerrima, O. sanctum, C. asiatica, M. charantia, Z. officinale, and W. somnifera in combination with ciprofloxacin and tetracycline showed synergistic antimicrobial activity with GIIs of 0.61-1.32 and GIIs 0.56-1.35 respectively. Methanolic extract of Z. officinal enhanced the antimicrobial potency of berberine (2 to 4-folds) and increased the EtBr accumulation. Furthermore, bioassay-guided fractionation leads to the identification of lariciresinol in ethyl acetate fraction, which decreased the MIC by 2-to 4-folds. The ΣFIC values varied from 0.30 to 0.55 with tetracycline, that indicated synergistic/additive effects. Lariciresinol also showed a good binding affinity with 6IE8 (-7.4 kcal mol-1) and 6IE9 (-8.2 kcal mol-1), which is comparable to tetracycline and chenodeoxycholic acid. Lariciresinol followed Lipinski's rule of five. CONCLUSION: The data suggest that lariciresinol from Z. officinale could be a potential efflux pump inhibitor that could lead to effective killing of drug resistant Salmonella typhimurium at lower MIC. Molecular docking confirmed the antibacterial EPI mechanism of lariciresinol in Salmonella typhimurium and confirmed to be safe for future use.

Phytocompounds from Himalayan Medicinal Plants as Potential Drugs to Treat Multidrug-Resistant Salmonella typhimurium: An In Silico Approach.

Medicinal plants can be used as natural therapeutics to treat diseases in humans. Enteric bacteria possess efflux pumps to remove bile salts from cells to avoid potential membrane damage. Resistance to bile and antibiotics is associated with the survival of Salmonella enterica subspecies enterica serovar Typhimurium (S. typhimurium) within a host. The present study aimed to investigate the binding affinity of major phytocompounds derived from 35 medicinal plants of the North Western Himalayas with the RamR protein (PDB ID 6IE9) of S. typhimurium. Proteins and ligands were prepared using AutoDock software 1.5.6. Molecular docking was performed using AutoDock Vina and MD simulation was performed at 100 ns. Drug likeness and toxicity predictions of hit phytocompounds were evaluated using molinspiration and ProTox II online servers. Moreover, docking, drug likeness, and toxicity results revealed that among all the selected phytocompounds, beta-sitosterol exhibited the most efficacious binding affinity with RamR protein (PDB ID 6IE9) and was nontoxic in nature. MD simulation data revealed that beta-sitosterol in complex with 6IE9 can be used as an antimicrobial. Furthermore, beta-sitosterol is stable in the binding pocket of the target protein; hence, it can be further explored as a drug to inhibit resistance-nodulation-division efflux pumps.

Host Cell and SARS-CoV-2-Associated Molecular Structures and Factors as Potential Therapeutic Targets.

Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus's spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism, pathogenesis and clinical outcome. Furthermore, several structural and non-structural proteins of the virus themselves are very critical in determining the clinical outcome following infection. Considering such critical role(s) of the abovementioned host cell receptors, associated proteases/factors and virus structural/non-structural proteins (NSPs), it may be quite prudent to therapeutically target them through a multipronged clinical regimen to combat the disease.

Perianal Paget's Disease-a Case Report and a Review of Current Diagnosis and Management.

Paget's disease is an intraepithelial adenocarcinoma arising from the apocrine gland component of the skin. Paget's disease is most common in the breast but extra mammary disease is also seen. Perianal Paget's disease is a rare form of extramammary disease with few cases reported in literature. It can be primary-arising from the skin or secondary-cutaneous metastases of anorectal or genitourinary malignancy. We hereby wish to report a case of perianal Paget's disease that presented as an eczematous lesion and was diagnosed incidentally on biopsy. After appropriate staging, the patient underwent wide local excision till negative margins were obtained. The resultant tissue defect was successfully covered by split-thickness skin grafting.

"Primary omental hydatid cyst": a rare entity.

Hydatid cyst is caused by the parasite Echinococcus granulosus commonly seen in temperate regions. Primary omental hydatid cyst is rare entity. Diagnosis can be achieved with contrast-enhanced computed tomography of abdomen and pelvis along with serology. Eosinophilia is a strong pointer to hydatid cyst as a differential diagnosis. Open or laparoscopic excision of the cyst along with medical therapy remains the treatment of choice.