Wound healing potential of Acacia catechu in streptozotocin-induced diabetic mice using in vivo and in silico approach.

Background and aim: Acacia catechu Wild. (Fabaceae) barks are traditionally used in the treatment of diabetes and wounds. Therefore, the objective of the present study was to evaluate the wound healing potential of the alcoholic extract of A. catechu (EAC) in streptozotocin-induced diabetic mice. Experimental procedures: EAC was first subjected to phytochemical estimations and standardization using (-) epicatechin as marker with the help of HPLC. Diabetes was induced in mice using streptozotocin and the wound healing potential of EAC was evaluated using excision and incision wound models on topical and oral treatment. Various biochemical parameters, in vivo antioxidants, cytokine profiling, VEGF, and histopathological examination were also performed. Further, molecular docking studies were performed using ligand (-) epicatechin on human inducible nitric oxide synthase. Results and conclusion: Phytochemically, EAC showed the presence of tannins, flavonoids, phenolic compounds, and saponins, while the content of (-) epicatechin was reported to be 7.81% w/w. The maximum healing of wounds (91.84 ± 1.10%) was observed in mice treated with a combination of both topical (10% gel) and oral (extract at 200 mg/kg) followed by topically and orally treated groups respectively after 14 days of treatment. These groups also showed significant restoration of altered biochemical parameters, antioxidant enzymes and cytokines. The molecular docking studies confirmed the role of (-) epicatechin in stabilizing the human inducible nitric oxide synthase with inhibitor showing binding energy of -8.31 kcal/mol. The present study confirmed the role of (-) epicatechin as a major marker in diabetic wound healing potential of A. catechu.

Laser ablative treatment of musicogenic epilepsy arising from dominant mesial temporal lobe: illustrative case.

BACKGROUND: Musicogenic epilepsy (ME) is a rare reflex epilepsy in which seizures are triggered by musical stimuli. Prior descriptions of ME have suggested localization to the nondominant temporal lobe, primarily in neocortex. Although resection has been described as a treatment for ME, other surgical modalities, such as laser ablation, may effectively disrupt seizure networks in ME while incurring comparatively lower risks of morbidity. The authors described the use of laser ablation to treat ME arising from the dominant mesial temporal structures. OBSERVATIONS: A 37-year-old woman with a 15-year history of drug-resistant ME was referred for surgical evaluation. Her seizures were triggered by specific musical content and involved behavioral arrest, repetitive swallowing motions, and word incomprehension. Diagnostic studies, including magnetic resonance imaging, single-photon emission computed tomography, magnetoencephalography, Wada testing, and stereoelectroencephalography, indicated seizure onset in the left (dominant) mesial temporal lobe. Laser interstitial thermal therapy was used to ablate the left mesial seizure onset zone. The patient was discharged on postoperative day two. At 18-month follow-up, she was seizure-free with no posttreatment neurological deficits. LESSONS: Laser ablation can be an effective treatment option for well-localized forms of ME, particularly when seizures originate from the dominant mesial temporal lobe.

An epigenomic shift in amygdala marks the transition to maternal behaviors in alloparenting virgin female mice.

Adults of many species will care for young offspring that are not their own, a phenomenon called alloparenting. However, in many cases, nonparental adults must be sensitized by repeated or extended exposures to newborns before they will robustly display parental-like behaviors. To capture neurogenomic events underlying the transition to active parental caring behaviors, we analyzed brain gene expression and chromatin profiles of virgin female mice co-housed with pregnant dams during pregnancy and after birth. After an initial display of antagonistic behaviors and a surge of defense-related gene expression, we observed a dramatic shift in the chromatin landscape specifically in amygdala of the pup-exposed virgin females compared to females co-housed with mother before birth, accompanied by a dampening of anxiety-related gene expression. This epigenetic shift coincided with hypothalamic expression of the oxytocin gene and the emergence of behaviors and gene expression patterns classically associated with maternal care. The results outline a neurogenomic program associated with dramatic behavioral changes and suggest molecular networks relevant to human postpartum mental health.

Antimicrobial Activity of Chlorhexidine and Herbal Mouthwash Against the Adherence of Microorganism to Sutures After Periodontal Surgery: A Clinical Microbiological Study.

Introduction: Chemical plaque control agents assist to eliminate plaque microorganisms. Therefore, the purpose of this research was to compare the effectiveness of a herbal mouthwash (HiOraTM) and a mouthwash containing 0.2% chlorhexidine in preventing bacteria from adhering to sutures in participants who had had periodontal flap surgery. Material and methods: 75 patients with chronic periodontitis were included in the study and divided into three groups. Plain water, herbal, and chlorhexidine mouthwashes were given after periodontal surgery, and sutures were removed on the eighthpostoperative day and sent for microbial analysis. Further plaque index (PI) and gingival index (GI) were recorded at baseline and on the eighthpostoperative day. Results: Different aerobic bacterial species were isolated, namely Staphylococcus aureus (S. aureus), coagulase-negative staphylococci (Cons), Escherechia coli (E. coli), Klebsiella bacteroides, and Streptococcus mutans (S. mutans). Significant differences were found among colony-forming units (CFUs) of bacterial species in different groups, and it is found that chlorhexidine mouthwash is quite effective against the adherence of microorganisms to sutures after periodontal surgery as compared to the control group and herbal mouthwash group. Herbal mouthwash has less antimicrobial activity when compared to chlorhexidine, but herbal mouthwash is highly effective against microbial adherence to sutures when compared to the control group (plain water). Significant variations between groups are shown in the PI and GI scores, indicating that chlorhexidine is successful in lowering the PI and GI scores and that herbal rinse is also helpful in reducing these scores, but to a lesser extent than chlorhexidine. Conclusion: According to the findings of this research, sutures are at risk for developing bacterial infections. However, the adhesion of microbes to sutures may be decreased with the adjunctive use of antimicrobial medicines such as chlorhexidine and herbal mouthwashes, which will result in improved wound healing. Herbal mouth rinses are effective in killing germs. However, chlorhexidine is far more effective in this regard.

Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats: an in silico and in vivo evidence of GABAergic action and cytokine inhibition.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg i.p.)- induced neuropathic pain in Wistar rats.Methods: Docking simulation studies were done on the three-dimensional (3D) structure of the GABAA and PPAR γ receptor for the binding of EA as well as punicalagin docking studies on TNF-α, and IL-6. The Present Study conceptualized a test battery to evaluate the behavioral, biochemical and histological changes.Results: Vincristine -induced significant cold allodynia, mechanical hyperalgesia, and functional deficit on 12th and 21st days. It also increased in the levels of TNF-α (Tumor necrosis factor-α), IL-6 (Interleukin-6), and MPO (Myeloperoxidase). Administration of PFE (100 and 300 mg/kg, p.o.), EA (50 mg/kg), and gabapentin (100 mg/kg) attenuated Vincristine-induced behavioral and biochemical changes significantly (P < .05). PFE showed better antinociceptive activity to EA. The histopathological evaluation also revealed the protective effects of PFE. Pretreatment of bicuculline (selective antagonist of GABAA receptors) reversed antinociceptive action of PFE, but administration of γ aminobutyric acid potentiated the action of PFE. PPAR-γ antagonist BADGE did not modify the effect of PFE. Docking results revealed that EA properly positioned into GABA and PPARγ binding site and acts as a partial agonist. Docking score of Punicalagin found to be - 9.02 kcal/mol and - 8.32 kcal/mol on IL-6 and TNFα respectively.Discussion: Conclusively, the attenuating effect of PFE may be attributed to the GABAergic system, cytokine inhibition, and anti-inflammatory activities.

Computational assessment of saikosaponins as adjuvant treatment for COVID-19: molecular docking, dynamics, and network pharmacology analysis.

Saikosaponins are major biologically active triterpenoids, usually as glucosides, isolated from Traditional Chinese Medicines (TCM) such as Bupleurum spp., Heteromorpha spp., and Scrophularia scorodonia with their antiviral and immunomodulatory potential. This investigation presents molecular docking, molecular dynamics simulation, and free energy calculation studies of saikosaponins as adjuvant therapy in the treatment for COVID19. Molecular docking studies for 23 saikosaponins on the crystal structures of the extracellular domains of human lnterleukin-6 receptor (IL6), human Janus Kinase-3 (JAK3), and dehydrogenase domain of Cylindrospermum stagnale NADPH-oxidase 5 (NOX5) were performed, and selected protein-ligand complexes were subjected to 100 ns molecular dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Molecular docking and molecular dynamics simulation studies revealed that IL6 in complex with Saikosaponin_U and Saikosaponin_V, JAK3 in complex with Saikosaponin_B4 and Saikosaponin_I, and NOX5 in complex with Saikosaponin_BK1 and Saikosaponin_C have good docking and molecular dynamics profiles. However, the Janus Kinase-3 is the best interacting partner for the saikosaponin compounds. The network pharmacology analysis suggests saikosaponins interact with the proteins CAT Gene CAT (Catalase) and Checkpoint kinase 1 (CHEK1); both of these enzymes play a major role in cell homeostasis and DNA damage during infection, suggesting a possible improvement in immune response toward COVID-19.

Sars-cov-2 host entry and replication inhibitors from Indian ginseng: an in-silico approach.

COVID-19 has ravaged the world and is the greatest of pandemics in modern human history, in the absence of treatment or vaccine, the mortality and morbidity rates are very high. The present investigation identifies potential leads from the plant Withania somnifera (Indian ginseng), a well-known antiviral, immunomodulatory, anti-inflammatory and a potent antioxidant plant, using molecular docking and dynamics studies. Two different protein targets of SARS-CoV-2 namely NSP15 endoribonuclease and receptor binding domain of prefusion spike protein from SARS-CoV-2 were targeted. Molecular docking studies suggested Withanoside X and Quercetin glucoside from W. somnifera have favorable interactions at the binding site of selected proteins, that is, 6W01 and 6M0J. The top-ranked phytochemicals from docking studies, subjected to 100 ns molecular dynamics (MD) suggested Withanoside X with the highest binding free energy (ΔGbind = -89.42 kcal/mol) as the most promising inhibitor. During MD studies, the molecule optimizes its conformation for better fitting with the receptor active site justifying the high binding affinity. Based on proven therapeutic, that is, immunomodulatory, antioxidant and anti-inflammatory roles and plausible potential against n-CoV-2 proteins, Indian ginseng could be one of the alternatives as an antiviral agent in the treatment of COVID 19. Communicated by Ramaswamy H. Sarma.

Potential Leads from Liquorice Against SARS-CoV-2 Main Protease using Molecular Docking Simulation Studies.

AIM AND OBJECTIVE: At present, the world is facing a global pandemic threat of SARSCoV- 2 or COVID-19 and to date, there are no clinically approved vaccines or antiviral drugs available for the treatment of coronavirus infections. Studies conducted in China recommended the use of liquorice (Glycyrrhiza species), an integral medicinal herb of traditional Chinese medicine, in the deactivation of COVID-19. Therefore, the present investigation was undertaken to identify the leads from the liquorice plant against COVID-19 using molecular docking simulation studies. MATERIALS AND METHODS: A set of reported bioactive compounds of liquorice were investigated for COVID-19 main protease (Mpro) inhibitory potential. The study was conducted on Autodock vina software using COVID-19 Mpro as a target protein having PDB ID: 6LU7. RESULTS: Out of the total 20 docked compounds, only six compounds showed the best affinity towards the protein target, which included glycyrrhizic acid, isoliquiritin apioside, glyasperin A, liquiritin, 1-methoxyphaseollidin and hedysarimcoumestan B. From the overall observation, glycyrrhizic acid followed by isoliquiritin apioside demonstrated the best affinity towards Mpro representing the binding energy of -8.6 and -7.9 Kcal/mol, respectively. Nevertheless, the other four compounds were also quite comparable with the later one. CONCLUSION: From the present investigation, we conclude that the compounds having oxane ring and chromenone ring substituted with hydroxyl 3-methylbut-2-enyl group could be the best alternative for the development of new leads from liquorice plant against COVID-19.

Identification of bioactive compounds from Glycyrrhiza glabra as possible inhibitor of SARS-CoV-2 spike glycoprotein and non-structural protein-15: a pharmacoinformatics study.

At present, the world is facing a pandemic named as COVID-19, caused by SARS-CoV-2. Traditional Chinese medicine has recommended the use of liquorice (Glycyrrhiza species) in the treatment of infections caused by SARS-CoV-2. Therefore, the present investigation was carried out to identify the active molecule from the liquorice against different protein targets of COVID-19 using an in-silico approach. The molecular docking simulation study of 20 compounds along with two standard antiviral drugs (Lopinavir and Rivabirin) was carried out with the help of Autodock vina software using two protein targets from COVID-19 i.e. spike glycoprotein (PDB ID: 6VSB) and Non-structural Protein-15 (Nsp15) endoribonuclease (PDB ID: 6W01). From the observed binding energy and the binding interactions, glyasperin A showed high affinity towards Nsp15 endoribonuclease with uridine specificity, while glycyrrhizic acid was found to be best suited for the binding pocket of spike glycoprotein and also prohibited the entry of the virus into the host cell. Further, the dynamic behavior of the best-docked molecules inside the spike glycoprotein and Nsp15 endoribonuclease were explored through all-atoms molecular dynamics (MD) simulation study. Several parameters from the MD simulation have substantiated the stability of protein-ligand stability. The binding free energy of both glyasperin A and glycyrrhizic acid was calculated from the entire MD simulation trajectory through the MM-PBSA approach and found to high binding affinity towards the respective protein receptor cavity. Thus, glyasperin A and glycyrrhizic acid could be considered as the best molecule from liquorice, which could find useful against COVID-19. Communicated by Ramaswamy H. Sarma.

An in-silico evaluation of different Saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets.

The Public Health Emergency of International Concern declared the widespread outbreak of SARS-CoV-2 as a global pandemic emergency, which has resulted in 1,773,086 confirmed cases including 111,652 human deaths, as on 13 April 2020, as reported to World Health Organization. As of now, there are no vaccines or antiviral drugs declared to be officially useful against the infection. Saikosaponin is a group of oleanane derivatives reported in Chinese medicinal plants and are described for their anti-viral, anti-tumor, anti-inflammatory, anticonvulsant, antinephritis and hepatoprotective activities. They have also been known to have anti-coronaviral property by interfering the early stage of viral replication including absorption and penetration of the virus. Thus, the present study was undertaken to screen and evaluate the potency of different Saikosaponins against different sets of SARS-CoV-2 binding protein via computational molecular docking simulations. Docking was carried out on a Glide module of Schrodinger Maestro 2018-1 MM Share Version on NSP15 (PDB ID: 6W01) and Prefusion 2019-nCoV spike glycoprotein (PDB ID: 6VSB) from SARS-CoV-2. From the binding energy and interaction studies, the Saikosaponins U and V showed the best affinity towards both the proteins suggesting them to be future research molecule as they mark the desire interaction with NSP15, which is responsible for replication of RNA and also with 2019-nCoV spike glycoprotein which manage the connection with ACE2. [Formula: see text] Communicated by Ramaswamy H. Sarma.

Effect of ethanolic extract of Solanum virginianum Linn. on neuropathic pain using chronic constriction injury rat model and molecular docking studies.

The present research work was designed to examine the neuroprotective effect of ethanolic extract of Solanum virginianum Linn. (SV) in chronic construction injury (CCI) of sciatic nerve-induced neuropathic pain in rats. The extract was initially standardized by high-performance thin-layer chromatography using solasodine as a biomarker and was then subjected to assess the degree of mechanical allodynia, thermal allodynia, mechanical hyperalgesia, thermal hyperalgesia and biochemical evaluations. Administration of SV (100 and 200 mg/kg; p.o.) and pregabalin (10 mg/kg; p.o.) as a reference standard significantly debilitated hyperalgesia and allodynia and notably restored the altered antioxidant level and pro-inflammatory cytokine (IL-1ß and TNF-α) expression in a dose-dependent manner. Further, to appraise the mechanistic approach of solasodine, docking simulation studies were done on the 3D structure of the voltage-gated N-type calcium channel (Cav 2.2), R-type calcium channel (Cav 2.3) and sodium channel (Nav 1.7), and the results revealed that solasodine properly positioned into Phe 19, Leu 32, Met 51 and Met 71 (FLMM pocket) of Cav 2.2 and Cav 2.3 and being a competitor of Ca2+/N-lobe it may inactivate these calcium channels but did not bind into the desired binding pocket of Nav 1.7. Thus, the study confirmed the role of solasodine as a major biomarker for the observed neuroprotective nature of Solanum virginianum.

The antidiarrhoeal evaluation of Psidium guajava L. against enteropathogenic Escherichia coli induced infectious diarrhoea.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Psidium guajava L. (Myrtaceae), commonly used as an edible fruit is traditionally used worldwide in treatment of various gastrointestinal problems including diarrhoea. The leaves of the plant have also been evaluated for antidiarrhoeal activity in various chemical induced diarrhoea models. OBJECTIVE: The main objective of the present study was to evaluate the potency of P. guajava leaves and its major biomarker quercetin against enteropathogenic Escherichia coli (EPEC) induced infectious diarrhoea using preclinical and computational model. MATERIAL AND METHODS: P. guajava alcoholic leaf extract (PGE) was initially standardized using HPLC taking quercetin as a biomarker and was then subjected to antidiarrhoeal evaluation on rats in an EPEC induced diarrhoea rat model. The study included assessment of various behavioral parameters, initially for 6 h and then for up to 24 h of induction which was followed by estimation of stool water content, density of EPEC in stools and blood parameters evaluation. The colonic and small intestinal tissues of the treated animals were subjected to various biochemical estimations, in vivo antioxidant evaluation, estimation of ion concentration, Na+/K+-ATPase activity, assessment of pro-inflammatory cytokines and histopathological studies. Further, the major biomarker off PGE, quercetin was subjected to molecular docking studies with Na+/K+-ATPase and EPEC. RESULTS: The results demonstrated a significant antidiarrhoeal activity of quercetin (50 mg/kg), PGE at 200 and 400 mg/kg, p.o., where quercetin and PFGE at 200 mg/kg, p.o. were found to be more prominent, as confirmed through higher % protection, water content of stools and density of EPEC in stools. PGE and its biomarker quercetin also significantly recovered the WBC, Hb, platelets loss and also revealed a significant restoration of altered antioxidants level, pro-inflammatory cytokines (IL-1ß and TNF-α) expression and had positive influence on Na+/K+-ATPase activity. The docking studies of quercetin with Na+/K+-ATPase showed favourable interactions and residues Glu 327, Ser 775, Asn 776, Glu 779 and Asp 804 of Na+/K+-ATPase were adequately similar to quercetin for donating ligands for binding, while quercetin was also found to terminate the linkage between mammalian cells and EPEC thus, preventing further infection from EPEC. CONCLUSION: Inhibition in intestinal secretion, reduced nitric oxide production and inflammatory expression along with reactivation of Na+/K-ATPase activity could be attributed to the observed antidiarrhoeal potential of PGE against infectious diarrhoea, where quercetin was confirmed to be the main contributing factor.

Quercetin a major biomarker of Psidium guajava L. inhibits SepA protease activity of Shigella flexneri in treatment of infectious diarrhoea.

The leaves of the plant Psidium guajava L. (Myrtaceae) has been traditionally used in treatment of various gastrointestinal disorders including diarrhoea and have also been reported for its potent antidiarrhoeal activity on various chemical induced diarrhoea models. The objective of our present study was to evaluate the potency of the leaf extract of the plant Psidium guajava (PGE) along with its major biomarker quercetin against Shigella flexneri-induced sub chronic model of infectious diarrhoea. PGE at 100, 200 and 400 mg/kg, p.o. and quercetin at 50 mg/kg, p.o. were administered to Shigella flexneri-induced diarrhoeal rats for five days and various behavioural parameters were evaluated on 1st, 3rd and 5th day of treatment. This was followed by assessment of stool water content, density of Shigella flexneri in stools and blood parameters examination. After treatment, colon and small intestine of rats was dissected and subjected to biochemical estimations, cytokine profiling, antioxidant evaluations, ion concentration determination, Na+/K+-ATPase activity and histopathology. Molecular docking studies on crystal structure of Secreted Extracellular Protein A (SepA) from Shigella flexneri with biomarker quercetin was also performed. PGE at 200 mg/kg followed by quercetin depicted maximum antidiarrhoeal potential, which was confirmed through diarrhoea score and % protection, while PGE at 400 mg/kg showed similar effect to PGE 200 mg/kg thus, the later may have ceiling effect. PGE and quercetin also significantly reduced the density of Shigella flexneri in stools, water content of stools and restored the alterations observed in blood parameters, antioxidant status and pro-inflammatory cytokines (IL-6 and TNF-α) expression. These parameters contributed in normalization of electrolyte balance, reactivation of Na+/K+-ATPase activity and repairing of epithelial tissue damage, confirmed through histopathology. Docking simulation studies revealed the role of quercetin in inactivating the protease activity of SepA, a protein secreted by Shigella, which disrupts epithelial barrier integrity during infection and also manages its signal production. Thus, the overall results confirmed the role of quercetin as a major biomarker for the observed antidiarrhoeal potential of P. guajava against Shigella flexneri induced infectious diarrhoea.

Evaluation of nationwide referral pathways, investigation and treatment of suspected cauda equina syndrome in the United Kingdom.

Purpose: Cauda equina syndrome (CES) is a spinal emergency with clinical symptoms and signs that have low diagnostic accuracy. National guidelines in the United Kingdom (UK) state that all patients should undergo an MRI prior to referral to specialist spinal units and surgery should be performed at the earliest opportunity. We aimed to evaluate the current practice of investigating and treating suspected CES in the UK. Materials and Methods: A retrospective, multicentre observational study of the investigation and management of patients with suspected CES was conducted across the UK, including all patients referred to a spinal unit over 6 months between 1st October 2016 and 31st March 2017. Results: A total of 28 UK spinal units submitted data on 4441 referrals. Over half of referrals were made without any previous imaging (n = 2572, 57.9%). Of all referrals, 695 underwent surgical decompression (15.6%). The majority of referrals were made out-of-hours (n = 2229/3517, 63.4%). Patient location and pre-referral imaging were not associated with time intervals from symptom onset or presentation to decompression. Patients investigated outside of the spinal unit experienced longer time intervals from referral to undergoing the MRI scan. Conclusions: This is the largest known study of the investigation and management of suspected CES. We found that the majority of referrals were made without adequate investigations. Most patients were referred out-of-hours and many were transferred for an MRI without subsequently requiring surgery. Adherence to guidelines would reduce the number of referrals to spinal services by 72% and reduce the number of patient transfers by 79%.

Emerging Transistor Technologies Capable of Terahertz Amplification: A Way to Re-Engineer Terahertz Radar Sensors.

This paper reviews the state of emerging transistor technologies capable of terahertz amplification, as well as the state of transistor modeling as required in terahertz electronic circuit research. Commercial terahertz radar sensors of today are being built using bulky and expensive technologies such as Schottky diode detectors and lasers, as well as using some emerging detection methods. Meanwhile, a considerable amount of research effort has recently been invested in process development and modeling of transistor technologies capable of amplifying in the terahertz band. Indium phosphide (InP) transistors have been able to reach maximum oscillation frequency (fmax) values of over 1 THz for around a decade already, while silicon-germanium bipolar complementary metal-oxide semiconductor (BiCMOS) compatible heterojunction bipolar transistors have only recently crossed the fmax = 0.7 THz mark. While it seems that the InP technology could be the ultimate terahertz technology, according to the fmax and related metrics, the BiCMOS technology has the added advantage of lower cost and supporting a wider set of integrated component types. BiCMOS can thus be seen as an enabling factor for re-engineering of complete terahertz radar systems, for the first time fabricated as miniaturized monolithic integrated circuits. Rapid commercial deployment of monolithic terahertz radar chips, furthermore, depends on the accuracy of transistor modeling at these frequencies. Considerations such as fabrication and modeling of passives and antennas, as well as packaging of complete systems, are closely related to the two main contributions of this paper and are also reviewed here. Finally, this paper probes active terahertz circuits that have already been reported and that have the potential to be deployed in a re-engineered terahertz radar sensor system and attempts to predict future directions in re-engineering of monolithic radar sensors.

The potency of eriosematin E from Eriosema chinense Vogel. against enteropathogenic Escherichia coli induced diarrhoea using preclinical and molecular docking studies.

The main objective of the present study was to evaluate the potential of eriosematin E (ECM) isolated from the roots of Eriosema chinense against enteropathogenic Escherichia coli (EPEC) induced diarrhoea. ECM isolated from the bioactive chloroform fraction of E. chinense was subjected to antidiarrhoeal evaluation on rats against diarrhoea, induced by the oral suspension of EPEC. The study included evaluation of behavioral parameters for 6 h and up to 24 h of induction, followed by estimation of water content, the density of EPEC in stools and evaluation of various blood parameters. Further, the colonic and small intestinal tissues were subjected to biochemical estimations, antioxidant evaluation, determination of ion concentration, Na+/K+ -ATPase activity, pro-inflammatory cytokines assessment and histopathology. Finally, the impact of ECM on Na+/K+-ATPase was studied through molecular docking studies. Significant antidiarrhoeal potential of ECM was demonstrated at 5 and 10 mg/kg, p.o., however, ECM at 10 mg/kg, p.o. was found to be more effective, as confirmed through higher % protection, density of EPEC in stools and water content of stools. ECM also significantly increased the level of WBC, Hb, platelets and revealed restoration of altered antioxidants, pro-inflammatory cytokines (IL-1ß and TNF-α) status and also reactivated the suppressed Na+/K+-ATPase activity, which was also confirmed through docking studies showing H-bonding of hydroxyl group of ECM with amino acids Asp 190, Asn 167 and Glu 169 thus, maintaining proper electrolyte balance and also prevented epithelial tissue damage. The overall effect of ECM may be attributed to the decline in the elevated level of cytokines, inhibition in nitric oxide production and reactivation of Na+/K+-ATPase activity resulting in reduced intestinal secretion.

Effects of green tea on miRNA and microbiome of oral epithelium.

Consumption of green tea (GT) extracts or purified catechins has shown the ability to prevent oral and other cancers and inhibit cancer progression in rodent models, but the evidence for this in humans is mixed. Working with humans, we sought to understand the source of variable responses to GT by examining its effects on oral epithelium. Lingual epithelial RNA and lingual and gingival microbiota were measured before and after 4 weeks of exposure in tobacco smokers, whom are at high risk of oral cancer. GT consumption had on average inconsistent effects on miRNA expression in the oral epithelium. Only analysis that examined paired miRNAs, showing changed and coordinated expression with GT exposure, provided evidence for a GT effect on miRNAs, identifying miRNAs co-expressed with two hubs, miR-181a-5p and 301a-3p. An examination of the microbiome on cancer prone lingual mucosa, in contrast, showed clear shifts in the relative abundance of Streptococcus and Staphylococcus, and other genera after GT exposure. These data support the idea that tea consumption can consistently change oral bacteria in humans, which may affect carcinogenesis, but argue that GT effects on oral epithelial miRNA expression in humans vary between individuals.

Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice.

Agonistic encounters are powerful effectors of future behavior, and the ability to learn from this type of social challenge is an essential adaptive trait. We recently identified a conserved transcriptional program defining the response to social challenge across animal species, highly enriched in transcription factor (TF), energy metabolism, and developmental signaling genes. To understand the trajectory of this program and to uncover the most important regulatory influences controlling this response, we integrated gene expression data with the chromatin landscape in the hypothalamus, frontal cortex, and amygdala of socially challenged mice over time. The expression data revealed a complex spatiotemporal patterning of events starting with neural signaling molecules in the frontal cortex and ending in the modulation of developmental factors in the amygdala and hypothalamus, underpinned by a systems-wide shift in expression of energy metabolism-related genes. The transcriptional signals were correlated with significant shifts in chromatin accessibility and a network of challenge-associated TFs. Among these, the conserved metabolic and developmental regulator ESRRA was highlighted for an especially early and important regulatory role. Cell-type deconvolution analysis attributed the differential metabolic and developmental signals in this social context primarily to oligodendrocytes and neurons, respectively, and we show that ESRRA is expressed in both cell types. Localizing ESRRA binding sites in cortical chromatin, we show that this nuclear receptor binds both differentially expressed energy-related and neurodevelopmental TF genes. These data link metabolic and neurodevelopmental signaling to social challenge, and identify key regulatory drivers of this process with unprecedented tissue and temporal resolution.

The Pathophysiology of Early Hypotension Following Epinephrine-containing Local Anesthetic Infiltration of the Nasal Mucosa in Patients Undergoing Endoscopic Transsphenoidal Hypophysectomy: A Prospective, Observational Study.

In patients undergoing endoscopic transsphenoidal hypophysectomy, the nasal mucosa is often infiltrated with local anesthetic solutions that contain epinephrine to aid hemostasis. This may, however, result in hemodynamic changes, especially hypotension. We characterized the cardiovascular changes using a LiDCOrapid monitor in 13 patients after the infiltration of 4% articaine containing 1:200,000 epinephrine. Nine (69%) had a >20% decrease in mean arterial pressure at a median time of 116 seconds after the infiltration of articaine with epinephrine. Analysis of the cardiac output data revealed that this was caused by a sustained reduction in systemic vascular resistance. The arterial blood pressure normalized over a period of 60 to 90 seconds secondary to increases in stroke volume and heart rate producing an elevation in cardiac output. Transient hypotension following the infiltration of epinephrine-containing local anesthetics may be caused by epinephrine stimulation of ß2-adrenoceptors producing vasodilation.

Synthesis and evaluation of novel analogues of mangiferin as potent antipyretic.

OBJECTIVE: To screen different analogues of mangiferin pharmacologically for antipyretic activity. METHODS: The naturally occurring xanthone glycoside mangiferin was isolated by column chromatography from the ethanolic extract of stem bark of Mangifera indica. Mangiferin was further converted to 5-(N-phenylamino methyleno) mangiferin, 5-(N-p-chlorophenylamino methyleno) mangiferin, 5-(N-2-methyl phenylamino methyleno) mangiferin, 5-(N-p-methoxy phenylamino methyleno) mangiferin, 5-(N, N-diphenylamino methyleno) mangiferin, 5-(N-α-napthylamino methyleno) mangiferin and 5-(N-4-methyl phenylamino methyleno) mangiferin analogues. The synthesized compounds were further screened for antipyretic activity along with mangiferin at a dose level of 100 and 200 mg/kg. Mangiferin and its analogues were characterized by melting point andR(f)value determination and through spectral technique like UV, IR, and NMR spectral analysis. RESULTS: The antipyretic activity of mangiferin as well as all analogues was found to be more significant in at higher dose ie. 200 mg/kg which was depicted through a decrease in rectal temperature up to 3 h. CONCLUSIONS: The antipyretic activity of mangiferin and its analogues may be attributed to inhibition in synthesis of TNF-α and anti-oxidant activity associated with amelioration of inflammatory actions of cytokines.