Methanolic fraction of Cassia fistula L. bark exhibits potential to combat oxidative stress and possess antiproliferative activity.

Cassia fistula L. is well known for its traditional medicinal properties as an anti-inflammatory, hepatoprotective, antifungal, antibacterial, antimutagenic, and wound healing agent. The aim of the present study was to determine antioxidant, genoprotective, and cytotoxic potential of different fractions of C. fistula bark including hexane (CaMH), chloroform (CaMC), ethyl acetate (CaME), and methanol (CaMM). Among all the fractions studied, CaMM exhibited maximal radical scavenging activity in antioxidant DPPH assay, Superoxide anion radical scavenging assay and nitric oxide radical scavenging assay displayed an IC50 value of 18.95, 29.41, and 13.38 µg/ml, respectively. CaMM fraction possessed the highest phenolic (130.37 mg gallic acid equivalent/g dry weight of extract) and flavonoid (36.96 mg rutin equivalent/g dry weight of fraction) content. Data demonstrated significant positive correlation between polyphenol levels and radical scavenging activity. Single cell gel electrophoresis (Comet assay) exhibited genoprotective potential of C. fistula bark fractions against DNA damage induced by hydrogen peroxide (H2O2) in human lymphocytes. CaMM fraction displayed highest protective ability against H2O2 induced-toxicity as evidenced by significant decrease in % tail DNA content from 30 to 7% at highest concentration (200 µg/ml). CaMM was found to be rich in catechin, gallic acid, chlorogenic acid, and kaempferol. The phenolic content and antioxidant ability of the fractions was markedly negatively correlated with H2O2- induced DNA damage in human lymphocytes. Cytotoxic potential was evaluated against dermal epidermoid carcinoma (A431), pancreatic (MIA PaCa-2) and brain glioblastoma (LN-18) cancer cell lines using MTT assay. Results showed that C. fistula bark fractions possessed highest toxicity against the skin carcinoma cells. CaMM fraction reduced over 50% cell growth at the concentration of 76.72 µg/ml in A431 cells. These findings suggest that fractions of C. fistula bark exhibit potential to be considered as therapeutic agents in various carcinomas.

Allele mining in gene encoding fc fragment of IgG receptor, transporter, alpha (FCGRT) and association of nucleotide variants with passive transfer of immunity in neonatal buffalo calves.

BACKGROUND: Neonatal Fc receptors (FcRn) mediate the transcytosis of IgG present in colostrum across absorptive gut epithelium of newborn calves. FcRn receptor is a heterodimer composed of two polypeptides encoded by FCGRT (Fc fragment of IgG Receptor Transporter neonatal) and B2M (Beta 2 microglobulin) genes. Polymorphism in FCGRT gene may have a bearing on absorption of colostral immunoglobulins by neonatal buffalo calves, thereby affecting their immune status and susceptibility to diseases. The primary aim of our study was to mine alleles and single nucleotide polymorphs in the FCGRT gene and determine their association with the levels of IgG in serum of neonatal buffalo calves. METHODS AND RESULTS: On the basis of serum IgG levels estimated by indirect ELISA in 80 newborn calves, 20 calves each with highest and lowest IgG concentration were selected to study polymorphism in the FCGRT gene. The exonic regions of this gene were amplified in nine fragments which were subjected to PCR-SSCP to detect variations followed by the sequencing of variants to locate the SNPs. A total of nine SNPs (7 in introns and 2 in exons) were detected in four polymorphic fragments. Association study based on Odds ratios (ORs) with 95% Confidence Interval (CIs) established that the SNP G40T in fragment 3 has a significant (P < 0.05) bearing on IgG level in serum of neonatal buffalo calves. CONCLUSION: Genetic variation in FCGRT gene in buffalo calves was found to be associated with their serum IgG levels in neonatal stage which may have implications in calf survival and growth vis-à-vis inadequate transfer of passive immunity.

Next-generation sequencing in the biodiversity conservation of endangered medicinal plants.

Medicinal plants have been used as traditional herbal medicines in the treatment of various types of diseases. However, the increased demand for these plants highlights the importance of conservation specifically for endangered species. Significant advancements in next-generation sequencing (NGS) technologies have accelerated medicinal plant research while reducing costs and time demands. NGS systems enable high-throughput whole genome sequencing as well as direct RNA sequencing and transcriptome analysis. The sequence data sets created can be used in a variety of areas of study, including biodiversity conservation, comparative genomics, transcriptomic analysis, single cell mining, metagenomics, epigenetics, molecular marker discovery, multi genome sequencing, and so on. Commercial sequencing service providers are constantly working to improve technologies to address bioinformatics problems in NGS data analysis. Several genome sequencing projects on medicinal plants have been completed recently and a few more are in the works. In some medicinal plants, massive NGS-based data has been developed. In the present review, we have attempted to briefly discuss advancements in NGS technology on medicinally essential plants in India. The review will also provide ideas for applying NGS technologies for exploring genomes of various endangered medicinal plants whose genome sequences are not normally available and thus provides valuable insights for the conservation of these vulnerable species.

A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer's Disease.

In the current study, for the first time, we study mitophagy enhancer urolithin A and a combination of urolithin A+green tea extract EGCG against human Aß peptide-induced mitochondrial and synaptic, dendritic, inflammatory toxicities and behavioral changes in humanized homozygous amyloid beta knockin (hAbKI) mice of late-onset Alzheimer's disease (AD). Our findings reveal significantly increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory. mRNA and protein levels of mitochondrial fusion, synaptic, mitophagy and autophagy genes were upregulated, and mitochondrial fission genes are downregulated in urolithin A and combine treatment in hAbKI mice; however, the effect is stronger in combined treatment. Immunofluorescence analysis of hippocampal brain sections shows similar findings of mRNA and protein levels. Mitochondrial dysfunction is significantly reduced in both treatment groups, but a stronger reduction is observed in combined treatment. Dendritic spines and lengths are significantly increased in both treatment groups, but the effect is stronger in combined treatment. The fragmented number of mitochondria is reduced, and mitochondrial length is increased, and mitophagosomal formations are increased in both the groups, but the effect is stronger in the combined treatment. The levels of amyloid beta (Aß) 40 and Aß42 are reduced in both treatments, however, the reduction is higher for combined treatment. These observations suggest that urolithin A is protective against human Aß peptide-induced toxicities; however, combined treatment of urolithin A+EGCG is effective and stronger, indicating that combined therapy is promising to treat late-onset AD patients.

Detection of nucleotide variants in FCGRT (Fc fragment of IgG, receptor, transporter, alpha) gene and their influence on colostral IgG concentration in Indian water buffalo (Bubalus bubalis).

BACKGROUND: The neonatal Fc receptors (FcRn) mediate the transfer of immunoglobulin G (IgG) molecules from a dam's circulation to the colostrum produced by it immediately after parturition. In ruminants, the calves born are agammaglobulinemic therefore, ingestion of colostrum with high concentration of IgG imparts passive immunity to the newborn. The FcRn molecule is a heterodimer, coded by FCGRT (Fc fragment of IgG Receptor Transporter neonatal) and B2M (Beta 2 microglobulin) genes. Present study attempted to identify single nucleotide polymorphisms (SNPs) in the FCGRT gene in 40 buffaloes of Murrah breed and evaluated the association of these nucleotide variations and haplotypes with IgG concentration in their colostrum. METHODS AND RESULTS: Animals producing colostrum with high IgG and low IgG levels were identified by indirect ELISA and selected. SNPs were detected in the FCGRT gene sequence of selected animals by amplifying it in nine fragments covering all exons (with flanking introns) followed by PCR-single strand conformational polymorphism (PCR-SSCP). A total of nine SNPs were observed of which seven were present in flanking introns and two in exon 4 of the gene. The SNP A75G was non-synonymous and produced an amino acid change from isoleucine to valine. The exonic SNPs and corresponding haplotypes were found to be significantly (P < 0.01 and 0.05 respectively) associated with colostral IgG concentration based on Odds ratios at 95% confidence interval. CONCLUSION: Polymorphism in FCGRT gene is found to be associated with IgG concentration in colostrum and identification of females with desirable variations may prevent failure of passive transfer in neonatal ruminants.

Yogic Neti-Kriya Using Povidone Iodine: Can it have a Preventive Role Against SARS-CoV-2 Infection Gateway?

During this COVID-19 pandemic, except steroid, none of the therapeutic measures have showed any evidence of efficacy. Traditionally jala-neti using lukewarm salted water remains a yogic way of maintaining upper airway hygiene. Saline irrigation decreases the concentration of inflammatory mediators (e.g. histamine, leukotriene etc.) in nasal secretions, reduces the severity and frequency of sinusitis, reduce need of antibiotic therapy and restores competency of nasal mucosa. Jala-neti is an integral part of six cleansing techniques of yogic kriyas practised in India since thousands of years. Jala-neti can clean the upper airways, prevents colonization of infectious agents, removes foreign bodies, prevents stasis of mucous and subsequently enhances the drainage of paranasal sinuses and maintain health. Regular practice of Jala neti improves nasal symptoms and overall health status of patients with sinusitis. Jala-neti sample can even be used for COVID-19 diagnosis. Povidone iodine (PVP-I) has been utilized as a time tested antimicrobial agent with broad spectrum coverage against wide range of bacteria and viruses. Anti-SARS-CoV-2 action of PVP-I was seen at a concentration as low as 0.45%. PVP-I is generally well tolerated upto 5%, however nasal ciliotoxicity is reported at this concentration, however, this toxicity is not reported with lower concentrations(1.25% and 0.5%). So, theoretically, by using neti-kriya with povidone iodine (0.5-1%) as irrigation solution can combine and enhance the protection against COVID-19 and this can be an important armor in the fight against COVID-19. However, this hypothesis needs to be validated in real life clinical trial scenario before implementing.

Current status of in silico, preclinical and clinical study registries across the globe: A systematic review and meta-analysis.

INTRODUCTION: Registration of study protocols brings about transparency and traceability and the amount of publication bias can be estimated. In this study, we have collected and presented data regarding clinical study registries, preclinical, in vitro and in silico study registries across the globe. MATERIALS AND METHODS: We searched via Google Search Engine with appropriate keywords e.g. name of country (n = 198), name of continent (n = 7), registry, study registry, animal, in silico, virtual, simulation, preclinical, animal, clinical trial. The overall pooled prevalence of clinical study registries and WHO primary registries in per continent was calculated using Medcalc software. RESULTS: The overall pooled prevalence of clinical study registries were 13% in each continent. The prevalence of WHO primary study registries were 8.9% of the countries per continent. Overall, there are 17 primary registries associated with WHO ICTRP as primary registries, 2 partner registries and 6 registries are affiliated to ICMJE. However, the amount of preclinical animal study registry was quite less (n = 4). Regarding in vitro studies, only country specific in vitro fertilization registries were available, however, in other research domains, registries were absent. Only one simulation study registry was available. CONCLUSION: At priori study registration is essential to deal with selective reporting. Comparison between study protocol and final report allows us to know the protocol deviations and allows us to evaluate risk of bias and internal validity of the research findings. Although trialists are responsible for the completeness of records, yet the registries must have some measures for their periodic update and quality control of the data.

Promising traditional Indian medicinal plants for the management of novel Coronavirus disease: A systematic review.

Traditional Indian medical practices (Ayurveda, Siddha, Unani, and homeopathy) are a vast reservoir of knowledge about medicinal plants. The promising pharmacological properties of these plants have paved the way for developing therapy against novel Coronavirus (CoV) infection. The current review will summarize published works of literature on the effects of traditional Indian medicinal plants against acute respiratory infection (COVID-19, SARS, Influenza, and Respiratory syncytial virus infection) and registered clinical trials of traditional Indian herbal medicines in COVID-19. The current study aims to comprehensively evaluate the data of traditional Indian medicinal plants to warrant their use in COVID-19 management. PubMed, Embase, and Cochrane databases were searched along with different clinical trial databases. A total of 22 relevant traditional Indian medicinal plants (35 relevant studies) were included in the current study having potential antiviral properties against virus-induced respiratory illness along with promising immunomodulatory and thrombolytic properties. Further, 36 randomized and nonrandomized registered clinical trials were also included that were aimed at evaluating the efficacy of herbal plants or their formulations in COVID-19 management. The antiviral, immunomodulatory, and thrombolytic activities of the traditional Indian medicinal plants laid down a strong rationale for their use in developing therapies against SARS-CoV-2 infection. The study identified some important potential traditional Indian medicinal herbs such as Ocimum tenuiflorum, Tinospora cordifolia, Achyranthes bidentata, Cinnamomum cassia, Cydonia oblonga, Embelin ribes, Justicia adhatoda, Momordica charantia, Withania somnifera, Zingiber officinale, Camphor, and Kabusura kudineer, which could be used in therapeutic strategies against SARS-CoV-2 infection.

Yoga-An Alternative Form of Therapy in Patients with Blunt Chest Trauma: A Randomized Controlled Trial.

BACKGROUND: Yoga as alternative form of therapy has shown positive impact on pulmonary functions, exercise capacity, behavioral changes, and inflammation in non-trauma patients. However, the efficacy of Yoga has not been studied in chest trauma patients. METHODS: This randomized controlled trial was conducted at level-1 Trauma Centre. Isolated chest injury patients were randomized into either standard physiotherapy or Yogatherapy groups. Patients in physiotherapy group received conventional chest physiotherapy and Yogatherapy group received a set of Yogic exercises in addition to conventional chest physiotherapy. Primary outcome measure was changes in pulmonary function tests (PFT) at 4 weeks of discharge. Secondary outcomes were changes in quality of life (QoL), respiratory muscle strength and endurance, chest wall mobility, and levels of cytokines at 4 weeks. Data were analyzed using STATA v14.0. RESULTS: A total of 89 eligible patients were randomized to physiotherapy (n = 46) and Yoga therapy (n = 43) groups. Demographic characteristics were comparable in both the groups. There were statistically significant improvements in PFT in the Yogatherapy group compared with physiotherapy with an increase in Forced vital capacity (p = 0.02) and Forced expiratory volume (p = 0.01) at 4 weeks. In addition, there were significant improvement in physical component of QoL, respiratory muscle endurance (p = 0.003) and axillary cirtometry (p = 0.009) in the Yogatherapy group. However, no statistically significant difference in the trends of cytokine markers seen between the groups. CONCLUSION: Yoga was found to be effective in improving pulmonary functions and QoL in patients with chest trauma. (Trial registered at ctri.nic.in/clinicaltrials/login.php, numberREF/2016/05/011,287).

Pharmacokinetics-Based Optimization of Phototherapy in Neonates Undergoing Treatment for Hyperbilirubinemia.

Introduction: Neonatal jaundice results from combined effects of both increased production of bilirubin and decreased hepatic excretory capacity in neonates. Since its discovery, phototherapy is the most widespread treatment used in neonatal jaundice. In this work, we try to search for a relationship between exposure to phototherapy and decrease in serum bilirubin (linearity vs proportionality). Methods:The present research was non-randomized prospective study conducted in the Neonatal Intensive Care Unit (NICU), Department of Paediatrics, AIIMS, New Delhi, and the Department of Pharmacology, AIIMS, New Delhi, India. Subjects were recruited from neonates admitted in NICU AIIMS, which meets our selection criteria. Infants were given a low dose of either phototherapy continuously or phototherapy for the first six hours and a double dose of phototherapy for the next six hours. Samples were collected before the beginning of the study (0 hours) and then at six and 12 hours. Bilirubin concentration was measured using HPLC and (LC-MS/MS). Results and conclusion:The percentage of reduction during the 6-12-hour interval was compared with that during the 0-6-hour interval if all experimental conditions were kept unchanged. A relationship curve between percentage of reduction and irradiance was created based on the percentage of reduction in serum bilirubin during the 0-6-hour and 0-12-hour intervals. The present study suggests that the relationship between efficacy, as measured by percentage of reduction in serum bilirubin, and irradiance is unlikely to be linear. Collected data are insufficient to clearly distinguish between proportionality and saturation point, considering that the results may be possible with both of these hypotheses.

Efficacy of green tea, its polyphenols and nanoformulation in experimental colitis and the role of non-canonical and canonical nuclear factor kappa beta (NF-kB) pathway: a preclinical in-vivo and in-silico exploratory study.

NF-kB plays a major role in the aetiopathogenesis of inflammatory-colitis. In this study, we evaluated the efficacy of green tea and its polyphenols and their nanoformulation in Tri-Nitro Benzene Sulfonic acid (TNBS) induced colitis in in-vivo system (Rat) and the involvement of non-canonical and canonical NF-kB pathway in green tea mediated protection (in-silico platform). We used the Wister rat model of TNBS-induced colitis. Rats were grouped into eleven groups (six animals each) and administered vehicle (ethanol), TNBS, Epicatechin (EC), Epigallocatechin (EGC), Epicatechin-gallate (ECG), Epigallocatechin-gallate (EGCG), sulfasalazine, green tea, EGCG + sulfasalazine, nano-EGCG and nano-EGCG + sulfasalazine for 14 days after induction of colitis. Colonic tissue was evaluated for the level of malondialdehyde, myeloperoxidase activity, catalase, reduced glutathione, glutathione peroxidase, IL-6, TNF-α, IL-1ß, NF-κB and morphological and histopathological evidence of damage. In the in-silico part, molecular docking and dynamic simulation study of EGCG was done against different targets in NF-kB for detailed evaluation of the role of non-canonical and canonical NF-KB pathway. In our study, EGCG reduced colonic inflammation, markers of oxidative stress, TNF-α, NF-κB, IL-1ß and IL-6. Nano-EGCG + sulfasalazine was more efficacious when compared to EGCG + sulfasalazine. In molecular docking and molecular dynamic simulation studies, EGCG showed a good binding profile to the inhibitor binding sites of IKK-beta, IKK-alpha and NIK. Thus, it can be concluded that EGCG showed protective action in experimental colitis acting through both non-canonical and canonical NF-kB pathway. Nano-EGCG + sulfasalazine combination showed better protection than nano-EGCG alone. Communicated by Ramaswamy H. Sarma.

Virtual screening and molecular dynamics study of approved drugs as inhibitors of spike protein S1 domain and ACE2 interaction in SARS-CoV-2.

BACKGROUND: The receptor binding domain (RBD) of spike protein S1 domain SARS-CoV-2 plays a key role in the interaction with ACE2, which leads to subsequent S2 domain mediated membrane fusion and incorporation of viral RNA into host cells. In this study we tend to repurpose already approved drugs as inhibitors of the interaction between S1-RBD and the ACE2 receptor. METHODS: 2456 approved drugs were screened against the RBD of S1 protein of SARS-CoV-2 (target PDB ID: 6M17). As the interacting surface between S1-RBD and ACE2 comprises of bigger region, the interacting surface was divided into 3 sites on the basis of interactions (site 1, 2 and 3) and a total of 5 grids were generated (site 1, site 2, site 3, site 1+site 2 and site 2+site 3). A virtual screening was performed using GLIDE implementing HTVS, SP and XP screening. The top hits (on the basis of docking score) were further screened for MM-GBSA. All the top hits were further evaluated in molecular dynamics studies. Performance of the virtual screening protocol was evaluated using enrichment studies. RESULT: and discussion: We performed 5 virtual screening against 5 grids generated. A total of 42 compounds were identified after virtual screening. These drugs were further assessed for their interaction dynamics in molecular dynamics simulation. On the basis of molecular dynamics studies, we come up with 10 molecules with favourable interaction profile, which also interacted with physiologically important residues (residues taking part in the interaction between S1-RBD and ACE2. These are antidiabetic (acarbose), vitamins (riboflavin and levomefolic acid), anti-platelet agents (cangrelor), aminoglycoside antibiotics (Kanamycin, amikacin) bronchodilator (fenoterol), immunomodulator (lamivudine), and anti-neoplastic agents (mitoxantrone and vidarabine). However, while considering the relative side chain fluctuations when compared to the S1-RBD: ACE2 complex riboflavin, fenoterol, cangrelor and vidarabine emerged out as molecules with prolonged relative stability. CONCLUSION: We identified 4 already approved drugs (riboflavin, fenoterol, cangrelor and vidarabine) as possible agents for repurposing as inhibitors of S1:ACE2 interaction. In-vitro validation of these findings are necessary for identification of a safe and effective inhibitor of S1: ACE2 mediated entry of SARS-CoV-2 into the host cell.

Antioxidant, Antiproliferative and Apoptosis-Inducing Efficacy of Fractions from Cassia fistula L. Leaves.

: Cassia fistula L. is a highly admirable traditional medicinal plant used for the treatment of various diseases and disorders. The present study was performed to divulge the antioxidant, antiproliferative, and apoptosis-inducing efficacy of fractions from C. fistula leaves. The hexane (CaLH fraction), chloroform (CaLC fraction), ethyl acetate (CaLE fraction), n-butanol (CaLB fraction), and aqueous (CaLA fraction) were sequentially fractionated from 80% methanolic (CaLM extract) of C. fistula leaves. The CaLE fraction was fractionated using column chromatography to yield a pure compound, which was characterized as Epiafzelechin (CFL1) based on 1H, 13C, and DEPT135 NMR. Among these fractions, CaLE and isolated CFL1 fractions exhibited an effective antioxidant potential in Ferric ion reducing power, (2,2'-azino-bis (3-ethylbenzothiazoline -6-sulfonic acid)) cation radical scavenging, and nitric oxide radical scavenging assays. Epiafzelechin was investigated for its antiproliferative effects against MG-63 (osteosarcoma), IMR-32 (neuroblastoma), and PC-3 (prostate adenocarcinoma), and was found to inhibit cell proliferation with a GI50 value of 8.73, 9.15, and 11.8 µM respectively. MG-63 cells underwent apoptotic cell death on treatment with Epiafzelechin as the cells showed the formation of apoptotic bodies, enhanced reactive oxygen species (ROS) generation, mitochondrial membrane depolarization along with an increase in early apoptotic cell population analyzed using Annexin V-FITC/PI double staining assay. Cells showed cell cycle arrest at the G0/G1 phase accompanied by a downregulation in the expression levels of p-Akt (Protein kinase B), p-GSK-3ß (Glycogen synthase kinase-3 beta), and Bcl-xl (B-cell lymphoma-extra large) proteins. RT-PCR (Real time-polymerase chain reaction) analysis revealed downregulation in the gene expression level of ß-catenin and CDK2 (cyclin-dependent kinases-2) while it upregulated the expression level of caspase-8 and p53 genes in MG-63 cells.

Multidrug-Resistant Candida auris Fungemia in Critical Care Units: Experience from a Tertiary Care Hospital in India.

Candida auris, a recently identified multiresistant Candida species, was first reported in Japan in 2009. It is different from other pathogenic yeast species because of its propensity to cause outbreaks and transmits between patients within health care settings. The invasive infections caused by C. auris are associated with high mortality rates, approaching 70% particularly in intensive care unit patients. Conventional biochemical methods are inaccurate in identifying this species of Candida. Although C. auris is frequently reported as multi-, extended-, or pan drug resistant to antifungal drugs, there is a wide variability in the susceptibility among reports worldwide. In this study we report a case series of five hospitalized patients with multidrug-resistant candidemia caused by C. auris in a tertiary hospital in India. Our finding suggests that correct identification followed by therapeutic intervention is necessary for favorable outcome in patients with C. auris fungemia.

Stable cellular models of nuclear receptor PXR for high-throughput evaluation of small molecules.

Pregnane & Xenobiotic Receptor (PXR) is one of the 48 members of the ligand-modulated transcription factors belonging to nuclear receptor superfamily. Though PXR is now well-established as a 'xenosensor', regulating the central detoxification and drug metabolizing machinery, it has also emerged as a key player in several metabolic disorders. This makes PXR attractive to both, researchers and pharmaceutical industry since clinical success of small drug molecules can be pre-evaluated on PXR platform. At the early stages of drug discovery, cell-based assays are used for high-throughput screening of small molecules. The future success or failure of a drug can be predicted by this approach saving expensive resources and time. In view of this, we have developed human liver cell line-based, dual-level screening and validation protocol on PXR platform having application to assess small molecules. We have generated two different stably transfected cell lines, (i) a stable promoter-reporter cell line (HepXREM) expressing PXR and a commonly used CYP3A4 promoter-reporter i.e. XREM-luciferase; and (ii) two stable cell lines integrated with proximal PXR-promoter-reporter (Hepx-1096/+43 and Hepx-497/+43). Employing HepXREM, Hepx-1096/+43 and Hepx-497/+43 stable cell lines > 25 anti-cancer herbal drug ingredients were screened for examining their modulatory effects on a) PXR transcriptional activity and, b) PXR-promoter activity. In conclusion, the present report provides a convenient and economical, dual-level screening system to facilitate the identification of superior therapeutic small molecules.

Protective Effects of Indian Spice Curcumin Against Amyloid-ß in Alzheimer's Disease.

The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-ß (Aß)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on Aß and curcumin has revealed that curcumin prevents Aß aggregation and crosses the blood-brain barrier, reach brain cells, and protect neurons from various toxic insults of aging and Aß in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin's bioavailability and urgent need for new formulations to increase its brain levels to treat patients with AD.

Modulation of genotoxicity of oxidative mutagens by glycyrrhizic acid from Glycyrrhiza glabra L.

BACKGROUND: The chemopreventive effects of certain phytoconstituents can be exploited for their use as functional foods, dietary supplements and even as drugs. The natural compounds, acting as anti-genotoxic and free radical scavenging compounds, may serve as potent chemopreventive agents. These can inhibit DNA modulatory activities of mutagens and help preventing pathological processes. OBJECTIVES: Present study on Glycyrrhiza glabra L., a promising medicinal plant, widely used in traditional medicine, focused on the bioassay-guided fractionation of its extracts for the isolation of certain phytochemicals with anti-genotoxic potential against oxidative mutagens. MATERIALS AND METHODS: The methanol extract of Glycyrrhiza glabra rhizomes was subjected to column chromatography, and isolated fraction was evaluated for its anti-genotoxic and antioxidant potential using SOS chromotest, Comet assay, and DPPH radical scavenging assay. RESULTS: GLG fraction, which was characterized as Glycyrrhizic acid, inhibited the genotoxicity of oxidative mutagens viz., H(2)O(2) and 4NQOquite efficiently. In SOS chromotest, using E.coli PQ37 tester strain, it inhibited induction factor induced by H(2)O(2) and 4NQO by 75.54% and 71.69% at the concentration of 121.46 µM,respectively. In Comet assay, it reduced the tail moment induced by H(2)O(2) and 4NQO by 70.21% and 69.04%, respectively, at the same concentration in human blood lymphocytes. The isolated fraction also exhibited DPPH free radical scavenging activity and was able to scavenge 85.95% radicals at a concentration of 120 µM. CONCLUSION: Glycyrrhizic acid is a potential modulator of genotoxins as well as efficient scavenger of free radicals.

Comparison of long-term outcome and quality of life after laparoscopic repair of incisional and ventral hernias with suture fixation with and without tacks: a prospective, randomized, controlled study.

BACKGROUND: Technique of mesh fixation in laparoscopic incisional hernia repair is a matter of debate. Literature is lacking in randomized trials comparing various methods of mesh fixation. This study was designed to compare the cost-effectiveness and long-term outcomes following the two methods of mesh fixation. METHODS: A total of 110 patients were randomized to tacker mesh fixation or suture mesh fixation. Patients with nonrecurrent hernias with defect size ranging from 2 to 5 cm were included. The cost and incremental cost-effectiveness ratio was calculated. SF-36v2 health survey was used for quality-of-life analysis. Patients were followed up at regular intervals, and return to activity and satisfaction scores were recorded. RESULTS: Demographic profile and hernia characteristics were comparable between the two groups. Operation time was significantly higher (p < 0) and early postoperative pain at 1 h, 6 h, and 1 month was significantly lower in the suture group. There was no significant difference in the incidence of chronic pain and seroma formation over a mean follow-up of 32.2 months. Cost of procedure was significantly higher in group I (p < 0.001). Suture fixation was found to be more cost-effective than tacker fixation. Postoperative quality of life outcomes were similar in the two groups. Among return to activity parameters, time to resumption of daily activities and starting climbing stairs were significantly shorter in the suture group. CONCLUSIONS: The suture fixation method is a cost-effective alternative to tacker fixation in patients with small- to medium-sized defects in laparoscopic incisional and ventral hernia repair. Suture fixation is better than tacker fixation in terms of early postoperative pain and return to activity. The two procedures are equally effective regarding the recurrence rates, complications, hospital stay, chronic pain, quality of life determinants, and patient satisfaction.