Antimicrobial Potential of Polyphenols: An Update on Alternative for Combating Antimicrobial Resistance.

The last decade has encountered an increasing demand for plant-based natural antibiotics. This demand has led to more research-based investigations for natural sources of antimicrobial agents and published reports demonstrating that plant extracts are widely applied in modern medicine, reporting potential activity that may be due to polyphenol compounds. Interestingly, the effects of polyphenols on the sensitivity of bacteria to antibiotics have not been well-studied. Hence, the current review encompasses the prospective application of plant-based phenolic extracts from plants of Indian origin. The emergence of resistance to antimicrobial agents has increased the inefficacy of many antimicrobial drugs. Several strategies have been developed in recent times to overcome this issue. A combination of antimicrobial agents is employed for the failing antibiotics, which restores the desirable effect but may have toxicity-related issues. Phytochemicals such as some polyphenols have demonstrated their potent activity as antimicrobial agents of natural origin to work against resistance issues. These agents alone or in combination with certain antibiotics have been shown to enhance the antimicrobial activity against a spectrum of microbes. However, the information regarding the mechanisms and structure-activity relationships remains elusive. The present review also focuses on the possible mechanisms of natural compounds based on their structure- activity relationships for incorporating polyphenolic compounds in the drug-development processes. Besides this work, polyphenols could reduce drug dosage and may diminish the unhidden or hidden side effects of antibiotics. Pre-clinical findings have provided strong evidence that polyphenolic compounds, individually and in combination with already approved antibiotics, work well against the development of resistance. However, more studies must focus on in vivo results, and clinical research needs to specify the importance of polyphenol-based antibacterials in clinical trials.

Unveiling the Latest Breakthroughs: A Comprehensive Review of the Therapeutic Activity and Safety Profile of Aloe vera.

The use of herbal drugs as alternative and complementary medicine has increased in popularity, raising concerns about their safety profile. Aloe vera, a plant with diverse therapeutic properties, has been extensively used for centuries. This review aims to assess the therapeutic activity and safety profile of Aloe vera. A comprehensive literature search was conducted to gather relevant information from various biomedical databases. The chemical composition, mechanism of action, and therapeutic activities of Aloe vera were analyzed. Aloe vera contains numerous active components such as vitamins, enzymes, minerals, sugars, lignin, saponins, and anthraquinones. Its mechanisms of action involve collagen synthesis, anti-inflammatory effects, immune modulation, laxative properties, and antiviral activity. Aloe vera has demonstrated potential therapeutic benefits in wound healing, diabetes management, liver and kidney protection, and glycemic control. However, it is essential to consider potential side effects, such as skin irritation and allergic reactions. This review provides evidence-based information to improve patient safety and promote informed decisions regarding the use of Aloe vera as a therapeutic agent.

Comprehensive Review on Herbal Medicine: Emphasis on Current Therapy and Role of Phytoconstituents for Cancer Treatment.

INTRODUCTION: Cancer poses a significant public health challenge in both developed and developing nations, with a rising global incidence of patients facing the threat of death due to abnormal cell proliferation. AIM: Review explores the utilization of different parts of herbal medicinal plants and their active pharmaceutical constituents in the prevention and treatment of various types of cancer. METHODOLOGY: Various anticancer medicinal plants have been identified, demonstrating their therapeutic effects by inhibiting cancer-stimulating enzymes and hormones, activating DNA repair processes, boosting the synthesis of protective stimulants, reducing the formation of free radicals, and enhancing individual immunity. Data for this study were gathered from diverse online bibliographic and databases, including Google, Google Scholar, Mendeley, Springer Link, Research Gate, and PubMed. RESULT: Herbal drugs have a huge contribution to the inhibition of the progression of cancer.A large volume of clinical studies has reported the beneficial effects of herbal medicines on the survival, immune modulation, and quality of life (QOL) of cancer patients, when these herbal medicines are used in combination with conventional therapeutics. CONCLUSION: The latest medicines for the clinical purpose (Above 50 %) are derived from herbal products. Furthermore, combination of these herbs with nanotechnology shows promise in treating specific carcinomas.

Changing Trends Towards Herbal Supplements: An Insight into Safety and Herb-drug Interaction.

Herbs have been used as sustenance and medicine for a very long time, often in conjunction with other prescribed medications. Even though they are thought to be natural and secure, many of these herbs can interact with other medications and cause potentially dangerous adverse effects or decrease the benefits of the medication. The complex and diverse pharmacological functions carried out by the active ingredients in herbs unavoidably alter the pharmacokinetics of chemical drugs when administered in vivo. Drug transporter expression has a direct impact on how medications are absorbed, distributed, metabolized, and excreted in living organisms. Changes in substrate pharmacokinetics can affect the effectiveness and toxicity of a drug when the active ingredients of a herb inhibit or stimulate the expression of transporters. By reviewing published clinical and preclinical studies, this review aims to raise awareness of herbdrug interactions and discuss their evidence-based mechanisms and clinical consequences. More clinical information on herb-drug interactions is required to make choices regarding patient safety as the incidence and severity of herb-drug interactions are rising due to an increase in the use of herbal preparations globally.This review seeks to increase understanding of herb-drug interactions and explore their evidence-based mechanisms and clinical implications by reviewing published clinical and preclinical studies. The incidence and severity of herb-drug interactions are on the rise due to an increase in the use of herbal preparations worldwide, necessitating the need for more clinical data on these interactions in order to make decisions regarding patient safety. Healthcare workers and patients will become more alert to potential interactions as their knowledge of pharmacokinetic herb-drug interactions grows. The study's objective is to raise readers' awareness of possible interactions between herbal supplements and prescription medications who regularly take them.

Multifaceted Neuroprotective Role of Punicalagin: A Review.

Millions of people worldwide are currently afflicted with neurologic conditions like a seizure, depression, stress, Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, the precise etiopathology of these diseases is still unknown. Substantial studies are being conducted to discover more treatments against these disorders because many patients do not experience the therapeutic benefits that would be expected from using existing pharmaceutical strategies. Herbal medicines which have been used in traditional medicine for millennia to treat various neurological problems are also being investigated and scientifically assessed. Punicalagin is a known polyphenol that has significant antioxidant, anti-inflammatory, anti-viral, anti-proliferative, and anti-cancer properties. Around the world, traditional use of herbal drugs is gaining wider acceptance as a part of complementary and alternative medicine. The scientific community should pay attention to these many neuroprotective pharmacodynamic activities of Punicalagin to create effective pharmacotherapeutic plans, as evidenced by mounting data in pre-clinical research investigations. The current review describes the recent studies on the pharmacological effects of Punicalagin in a variety of neurological illnesses and paves the way for further study in this field.

Exploring the Role of Mentha in Gut Microbiota: A Modern Perspective of an Ancient Herb.

Gut microbiota includes the microbes present in the gut; these microbes are an essential component in maintaining a healthy gut. Gut microbiota has a wide range of functions, including effects on colonization, pathogen resistance, intestinal epithelial maintenance, metabolizing food and pharmaceutical chemicals, and influencing immunological functions. Every disease associated with the gut starts due to a disbalance in the composition of the gut microorganisms and can be managed by balancing the composition of gut bacteria using various herbal remedies. Mentha herbs are a variety of perennial herbs that are grown commercially in various parts of the world. Mentha is a potent herb that shows anticholinergic action and can block PGE2 and GM1 receptors and interact with cholera toxins; it is used traditionally in different systems of medicines to treat various gastrointestinal diseases associated with the gut. Mentha herbs have potent bactericidal, viricidal, and fungicidal properties. Mentha has been used to cure stomach and digestion issues as well as to treat a variety of disorders. This review article summarizes diseases associated with the gut, the composition, and function of gut microbiota, and mentha's effectiveness along with its extraction methods and traditional uses. Research findings revealed that mentha could be an essential source against a wide range of diseases, especially gastrointestinal disorders. From its ayurvedic claims to its present use, various confirmed its clinically effective for human health. The present work also describes the mechanism of action along with the bioactives present in this well-known herb from Ayurveda.

Compendium of naringenin: potential sources, analytical aspects, chemistry, nutraceutical potentials and pharmacological profile.

Naringenin is flavorless, water insoluble active principle belonging to flavanone subclass. It exhibits a diverse pharmacological profile as well as divine nutraceutical values. Although several researchers have explored this phytoconstituent to evaluate its promising properties, still it has not gained recognition at therapeutic levels and more clinical investigations are still required. Also the neutraceutical potential has limited marketed formulations. This compilation includes the description of reported therapeutic potentials of naringenin in variety of pathological conditions alongwith the underlying mechanisms. Details of various analytical investigations carried on this molecule have been provided along with brief description of chemistry and structural activity relationship. In the end, various patents filed and clinical trial data has been provided. Naringenin has revealed promising pharmacological activities including cardiovascular diseases, neuroprotection, anti-diabetic, anticancer, antimicrobial, antiviral, antioxidant, anti-inflammatory and anti-platelet activity. It has been marketed in the form of nanoformulations, co-crystals, solid dispersions, tablets, capsules and inclusion complexes. It is also available in various herbal formulations as nutraceutical supplement. There are some pharmacokinetic issue with naringenin like poor absorption and low dissolution rate. Although these issues have been sorted out upto certain extent still further research to investigate the bioavailability of naringenin from herbal supplements and its clinical efficacy is essential.

A comprehensive compiled review is presented on source, health benefits, chemistry and analysis, and marketed products of naringenin.Naringenin is a promising phytoconstituent as nutraceutical.Valorization of fruit peels of citrus fruits is a critical step for food and nutraceutical industry.Structure-activity relationship of naringenin derivatives.Nano-formulations incorporating naringenin in themselves can be used for targeted delivery for critical disorders.Naringenin obtained from the peels can be efficiently used in breads, cookies, cakes and other food products.

Treatment Opportunities and Technological Progress Prospective for Acne Vulgaris.

A frequent inflammatory pilosebaceous disorder that affects 80-90% of teenagers, acne vulgaris is still a concern for dermatologists and other doctors in the field of medicine. Acne has a significant psychosocial impact and is responsible for a bigger worldwide burden of disease than psoriasis, cellulitis, and melanoma, as measured by age-standardized disability-adjusted life years. Patients may experience psychological problems as well as severe skin scars as a result of the condition. The pathogenesis process of acne lesion is complex, so it is myriad of available treatment. Acne is caused by a combination of four different pathological causes, including an increase in sebum production, irregular follicular desquamation, P.acnes proliferation, and inflammation of the afflicted skin. Synthetic, hormonal, and herbal treatments, as well as their efficacy in treating acne vulgaris, are discussed in this article. The laser and light treatment for acne vulgaris available within a specific wavelength range that stimulates type I and III collagen and elastic fibres is described in relation to radiation therapies. The innovative drug delivery techniques are covered here, such as particle, vesicular, and colloidal delivery systems as a prospective therapy. We will present a practical method for acne management in this article and discuss how to assess acne, how to use topical therapies, and how systemic therapy can be used to treat acne. This review will inform readers on the most recent advances in our understanding of acne treatment-related technological potential, with a particular emphasis on developing treatment alternatives and creative ways that can assist improve patient results. Acne has been the subject of substantial research, both in terms of disease mechanism and therapeutic approaches. However, as Propionibacterium acnes develop resistance to current medications there is a requirement for novel therapeutic modalities. Additionally, the absence of required data regarding the efficacy of complementary and alternative medicine (CAM) therapies needs a greater investigation into these treatment choices.

ASIA syndrome with severe lupus - A case report.

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), also known as Shoenfeld's syndrome, encompasses several autoimmune conditions/phenomena that are triggered following the exposure to materials with an adjuvant activity known to augment an antigen-driven immune response. In some inherently vulnerable patients, they act as second hits to trigger or unmask an autoimmune disorder which ranges from generalized non-specific constitutional symptoms, and autoantibody production, to a new onset, of a fully-fledged autoimmune syndrome. In this manuscript, we present a case of a 37-year-old lady who developed systemic lupus erythematosus characterized by mucocutaneous, musculoskeletal, hematological neurological, and renal involvement a few years after silicone breast implants.

An Overview of Phytotherapy Used in the Management of Type II Diabetes.

Diabetes mellitus is related to unconstrained high blood sugar and linked with long-term impairment, dysfunction and failure of several organs. Since 1980, the global frequency of diabetes has almost doubled in the adult population. In very rare cases due to poor prevention and management programs, diabetes causes worsening of health and reduced lifespan of the world population, thus impacting on the world's economy. Supplements, however, help in the improvement of nutritional deficiencies. Phytotherapeutics has the advantage of being economical and easy to access with marginal side effects. So, it is a preferred candidate for the management of diabetes. Currently, a multitude of pharmaceuticals are used which are obtained from natural sources having medicinal properties. The mechanistic approaches are based on the regulation of insulin signaling pathways, translocation of GLUT-4 receptors and/or activation of PPAR γ. These natural compounds include numerous flavonoids which help in preventing glucose absorption by preventing the absorption of α-amylase and α-glucosidase. But to validate the efficacy and safety profile of these compounds, detailed validatory clinical studies are required. This review majorly focuses on the mechanistic approaches of various naturally derived compounds relevant for the condition of Diabetes Mellitus.

A multimodal quality improvement approach to promote normothermia in very preterm infants.

AIM: To achieve the National Neonatal Audit Programme (NNAP) standard of 90% normothermia among preterm infants born under 30 weeks of gestation. METHODS: Project SHIP (Stopping Hypothermia In Premmies) was a quality improvement programme to improve admission normothermia. Phase 1 of the project implemented low-fidelity simulations during 2011-2016. In Phase 2 (2017), a multimodal approach to quality improvement was used, including in situ simulations, videos of simulated scenarios, an allocated team member for thermal care, a clear protocol for thermal care, a coordinating 'lollipop man' role and monthly performance feedback. Additionally, continuous temperature monitoring using servo-control during stabilisation was introduced during Phase 2. Phase 3 (2018-2019) focused on embedding practice and maintaining performance. RESULTS: Phase 1 initiatives resulted in improvement of normothermia rates from 58% to 75%. However, the results plateaued. During Phase 2, the hypothermia rate fell from 16% to 3%. During Phase 3, this improvement in the hypothermia rate was sustained, achieving the standard of 90% normothermia in 2018 and falling just short in 2019 due to an increased hyperthermia rate. CONCLUSION: A multimodal quality improvement approach achieved sustained improvement in normothermia. Continuous temperature monitoring during stabilisation allows resuscitating teams to plan interventions to treat hypothermia and hyperthermia.

A pilot study for treatment of COVID-19 patients in moderate stage using intravenous administration of ozonized saline as an adjuvant treatment-registered clinical trial.

OBJECTIVE: Ozone therapy has tremendous therapeutic potential owing to its antiviral, anti-inflammatory and antioxidant properties, and potential to improve oxygenation. A pilot clinical trial was conducted to evaluate the safety and efficacy ofintravenous ozonised saline treatment in patients with moderate COVID-19 pneumonia. PATIENTS AND METHODS: 10 patients were administered 200 ml freshly prepared ozonised saline intravenously over 1 h once a day for 8 days along with standard medical treatment. Clinical symptoms were monitored everyday and laboratory biomarkers, radiological findings at 1,3,6,10 days. Telephonic follow up was done for all after discharge till Day 14. 7 out of 10 patients required oxygen supplementation at recruitment. RESULTS: There was severe adverse event recorded in the study group.All patients improved from moderate to mild category in average 8 days and were discharged in average 9.7 days. None deteriorated to severe stage. All clinical symptoms resolved within 6 days and oxygen supplementation requirement reduced to none within 4.1 days. There wasstatistically significant reduction inCRP (p = 0.003), D-Dimer (p = 0.049), IL6 (p = 0.002)and statistically significant improvement (p = 0.001) in SpO2/FiO2 ratio. Change in LDH was borderline statistically not significant (p = 0.058).All patients showed significant resolution of bilateral interstitial infiltrates at the end of 10 days. CONCLUSION: Resolved clinical symptoms, improved oxygenation, clearance of infiltrates on Chest X-ray and improvement in biomarkers in a short period with non-progression of the disease showed that IV ozonised saline therapy was safe and effective to prevent disease progression in COVID-19, making it an effective novel therapeutic tool.

Kidney transplant dysfunction in a patient with COVID - 19 infection: role of concurrent Sars-Cov 2 nephropathy, chronic rejection and vitamin C-mediated hyperoxalosis: case report.

BACKGROUND: COVID-19 infection in kidney transplant recipients often lead to allograft dysfunction. The allograft injury has various histopathological manifestations. Our case illustrates the unusual combination of allograft rejection, acute kidney injury secondary to oxalate nephropathy and SARS CoV-2 nephropathy as the cause of irreversible allograft failure. CASE PRESENTATION: A 56 year old renal allograft recipient presented with a history of fever and diarrhoea for the preceding 4 weeks, tested positive for Sars-CoV2 on nasal swab and was found to have severe allograft dysfunction, necessitating haemodialysis. He subsequently underwent an allograft biopsy, which demonstrated antibody mediated rejection along with the presence of extensive oxalate deposition in the tubules. Ultrastructural examination demonstrated spherical spiked particles in the glomerular capillary endothelium and the presence of tubulo-reticular inclusions suggestive of an active COVID-19 infection within the kidney. The intra-tubular oxalate deposition was considered to be the result of high dose, supplemental Vitamin C used as an immune booster in many patients with COVID - 19 infection in India. CONCLUSIONS: This case highlights the complex pathology that may be seen in following COVID-19 disease and the need for kidney biopsies in these patients to better understand the aetiology of disease.

Exploring scientific validation of Triphala Rasayana in ayurveda as a source of rejuvenation for contemporary healthcare: An update.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayurveda remains the classical and comprehensive part of the ancient Indian medicine system for well-being promotive, disease preventive, and revival approach for the human body. Triphala Rasayana is mentioned in Ayurveda, comprising fruits of three plant species viz. Phyllanthus emblica L. (P. emblica), Terminalia chebula Retz (T. chebula), and Terminalia bellirica Roxb (T.bellirica). Triphala Rasayana has been utilized in various traditional medicine systems, viz., Ayurveda, Siddha, and Unani. Traditionally Rasayana based drugs are utilized in different kinds of diseases without pathophysiological associations as indicated by current medication. Various medicinal attributes of Triphala Rasayana include antioxidant, anticancer, antidiabetic, antimicrobial, immunomodulatory, and anticataract and is also considered as a pillar for gastrointestinal treatment, specifically in functional gastrointestinal disorders (FGIDs). Due to Rasayana's accessible mode of administration, availability, and affordability, there is an increase in its global acceptance. AIM OF REVIEW: This review article summarizes the scientific validation, traditional uses, bioactive compounds, and ethnopharmacological properties of Triphala Rasayana. It also documents recent data on in vivo and in vitro pharmacological studies and clinical effects of Triphala Rasayana. MATERIAL AND METHOD: A literature review is carried out using PubMed, ScienceDirect, Scopus, web of science, Ayush Research Portal, and Clinical Trials Registry-India. In addition to an electronic search, traditional ayurvedic texts and books were used as sources of information. RESULTS: Traditionally, "Triphala Rasayana" is classified as a tridoshic rasayana and one of the most well-studied ayurvedic Rasayana. It showed various pharmacological activities such as anticancer, antioxidant, antibacterial, immunomodulatory, cardioprotective, and antidiabetic. Besides this, Rasayana has reported ethnopharmacological activities such as antimicrobial, anticataract, wound healing, and radioprotection. It has shown a good impact on the gastrointestinal tract (GIT) system with the reported pharmacological activities in gastrointestinal disorders such as constipation, gastric ulcer, and inflammatory bowel disease (IBD). Phytochemical studies of Triphala Rasayana revealed chemical constituents like gallic acid, ellagic acid, chebulic acid, chebulinic acid, methyl gallate, emblicanin A, and emblicanin B. Additionally, clinical studies found Triphala Rasayana to be effective against diabetes, constipation, and obesity. CONCLUSION: The present review revealed that Triphala Rasayana may treat a diverse range of diseases, especially GIT disorders. Considering the beneficial properties of Triphala Rasayana and it's proven non-toxic nature could be a source of rejuvenation in contemporary healthcare. Nevertheless, its clinical data effectively provided precious signals to correlate ayurvedic biology and modern medicine.

Renal Tubular Acidosis and Hypokalemic Paralysis as a First Presentation of Primary Sjögren's Syndrome.

Sjögren's syndrome is an autoimmune disease with multisystem involvement and varying clinical presentation. We report the clinical course and outcome of a case who presented with repeated episodes of hypokalemia mimicking hypokalemic periodic paralysis and metabolic acidosis, which was later diagnosed as distal renal tubular acidosis secondary to primary Sjögren's syndrome. A 50-year-old lady, who was previously diagnosed as hypokalemic periodic paralysis, presented with generalized weakness and fatigue. She was found to have severe hypokalemia with normal anion-gap metabolic acidosis consistent with distal renal tubular acidosis. Subsequent evaluation revealed Sjögren's syndrome as the cause of her problems. Kidney biopsy done to evaluate significant proteinuria revealed nonproliferative morphology with patchy acute tubular injury and significant chronic interstitial nephritis. The patient responded well to potassium supplementation and oral prednisolone. Presentation of this case highlights the necessity of close vigilance while managing a case of repeated hypokalemia, which could be one of the rare clinical manifestations of Sjögren's syndrome.

A new parameter tuning approach for enhanced motor imagery EEG signal classification.

A brain-computer interface (BCI) system allows direct communication between the brain and the external world. Common spatial pattern (CSP) has been used effectively for feature extraction of data used in BCI systems. However, many studies show that the performance of a BCI system using CSP largely depends on the filter parameters. The filter parameters that yield most discriminating information vary from subject to subject and manually tuning of the filter parameters is a difficult and time-consuming exercise. In this paper, we propose a new automated filter tuning approach for motor imagery electroencephalography (EEG) signal classification, which automatically and flexibly finds the filter parameters for optimal performance. We have evaluated the performance of our proposed method on two public benchmark datasets. Compared to the existing conventional CSP approach, our method reduces the average classification error rate by 2.89% and 3.61% for BCI Competition III dataset IVa and BCI Competition IV dataset I, respectively. Moreover, our proposed approach also achieved lowest average classification error rate compared to state-of-the-art methods studied in this paper. Thus, our proposed method can be potentially used for developing improved BCI systems, which can assist people with disabilities to recover their environmental control. It can also be used for enhanced disease recognition such as epileptic seizure detection using EEG signals. Graphical abstract ᅟ.

An open-label proof-of-concept study of intrathecal autologous bone marrow mononuclear cell transplantation in intellectual disability.

BACKGROUND: The underlying pathophysiology in intellectual disability (ID) involves abnormalities in dendritic branching and connectivity of the neuronal network. This limits the ability of the brain to process information. Conceptually, cellular therapy through its neurorestorative and neuroregenerative properties can counteract these pathogenetic mechanisms and improve neuronal connectivity. This improved networking should exhibit as clinical efficacy in patients with ID. METHODS: To assess the safety and efficacy of cellular therapy in patients with ID, we conducted an open-label proof-of-concept study from October 2011 to December 2015. Patients were divided into two groups: intervention group (n = 29) and rehabilitation group (n = 29). The intervention group underwent cellular transplantation consisting of intrathecal administration of autologous bone marrow mononuclear cells and standard neurorehabilitation. The rehabilitation group underwent only standard neurorehabilitation. The results of the symptomatic outcomes were compared between the two groups. In the intervention group analysis, the outcome measures used were the intelligence quotient (IQ) and the Wee Functional Independence Measure (Wee-FIM). To compare the pre-intervention and post-intervention results, statistical analysis was done using Wilcoxon's matched-pairs test for Wee-FIM scores and McNemar's test for symptomatic improvements and IQ. The effect of age and severity of the disorder were assessed for their impact on the outcome of intervention. Positron emission tomography-computed tomography (PET-CT) brain scan was used as a monitoring tool to study effects of the intervention. Adverse events were monitored for the safety of cellular therapy. RESULTS: On symptomatic analysis, greater improvements were seen in the intervention group as compared to the rehabilitation group. In the intervention group, the symptomatic improvements, IQ and Wee-FIM were statistically significant. A significantly better outcome of the intervention was found in the paediatric age group (<18 years) and patients with milder severity of ID. Repeat PET-CT scan in three patients of the intervention group showed improved metabolism in the frontal, parietal cortex, thalamus, mesial temporal structures and cerebellum. No major adverse events were witnessed. CONCLUSIONS: Cellular transplantation with neurorehabilitation is safe and effective for the treatment of underlying brain deficits in ID. TRIAL REGISTRATION: ClinicalTrials.gov NCT02245724. Registered 12 September 2014.

Pharmacological Review on Asiatic Acid and Its Derivatives: A Potential Compound.

Natural triterpenes represent a group of pharmacologically active and structurally diverse organic compounds. The focus on these phytochemicals has been enormous in the past few years, worldwide. Asiatic acid (AA), a naturally occurring pentacyclic triterpenoid, is found mainly in the traditional medicinal herb Centella asiatica. Triterpenoid saponins, which are the primary constituents of C. asiatica, are commonly believed to be responsible for their extensive therapeutic actions. Published research work has described the molecular mechanisms underlying the various biological activities of AA and its derivatives, which vary for each chronic disease. However, a compilation of the various pharmacological properties of AA has not yet been done. Herein, we describe in detail the pharmacological properties of AA and its derivatives that inhibit multiple pathways of intracellular signaling molecules and transcription factors that are involved in the various stages of chronic diseases. Furthermore, the pharmacological activities of AA were compared with two natural compounds: curcumin and resveratrol. This review summarizes the research on AA and its derivatives and helps to provide future directions in the area of drug development.

Is It Adverse, Nonadverse, Adaptive, or Artifact?

One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a nonadverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA. The lectures at this course provided guidance on determining and communicating adversity using case studies involving both clinical pathology and anatomic pathology. In addition, one talk also focused on data quality, study design, and interpretation of artifacts that could hinder the determination of adversity. The CE course ended with a talk on understanding adversity in preclinical studies and engaging the regulatory agencies in the decision-making process. This manuscript is designed to provide brief summaries of all the talks in this well-received CE course.

Improving protein fold recognition and structural class prediction accuracies using physicochemical properties of amino acids.

Predicting the three-dimensional (3-D) structure of a protein is an important task in the field of bioinformatics and biological sciences. However, directly predicting the 3-D structure from the primary structure is hard to achieve. Therefore, predicting the fold or structural class of a protein sequence is generally used as an intermediate step in determining the protein's 3-D structure. For protein fold recognition (PFR) and structural class prediction (SCP), two steps are required - feature extraction step and classification step. Feature extraction techniques generally utilize syntactical-based information, evolutionary-based information and physicochemical-based information to extract features. In this study, we explore the importance of utilizing the physicochemical properties of amino acids for improving PFR and SCP accuracies. For this, we propose a Forward Consecutive Search (FCS) scheme which aims to strategically select physicochemical attributes that will supplement the existing feature extraction techniques for PFR and SCP. An exhaustive search is conducted on all the existing 544 physicochemical attributes using the proposed FCS scheme and a subset of physicochemical attributes is identified. Features extracted from these selected attributes are then combined with existing syntactical-based and evolutionary-based features, to show an improvement in the recognition and prediction performance on benchmark datasets.