Genetic diversity, population structure and marker-trait associations in Indian kale (Brassica oleracea L. gp. acephala) using cross-species microsatellite markers.

Kale is known for its exceptional nourishing and functional benefits to human body. However, it is an understudied species from genomic as well as agronomic aspects. It is important to characterize niche kale germplasms around the world to systematically conserve and utilize its genetic variability, especially for commercial traits in the interest of growers, consumers and industry. With this view, genomic and phenotypic characterizations of 62 Kashmiri kale accessions including popular landraces were done to estimate and partition genetic diversity, understand trait relationships, develop population structure and divulge marker-trait associations of economic significance. Sixty-six cross species microsatellite (SSR) markers within Brassica genus amplified 269 alleles in the germplasm. Their polymorphic information content (PIC) ranged from 0.00078 to 0.953 with an average of 0.407. The population structure analysis and neighbour joining tree clustering categorized the germplasm into three sub-populations. AMOVA revealed more within-population variance (67.73 %) than among-populations (32.27 %) variance. The principal component analysis (PCA) involving 24 agronomical traits revealed seven PCs (PC1 to PC7) having Eigen values more than 1, which explained a cumulative variation of 69.21 %. Association mapping with respect to these 24 agronomical traits using mixed linear model and general linear model revealed six overlapping significant marker-trait relationships with five being significant at probability value of 0.001/0.0001. The highly significant associations of two SSRs with economically important traits (siliqua length and seed weight) significantly correlated/related with leaf yield and seed yield were revealed for their possible utilization in marker assisted breeding for higher leaf and seed yields.

Studies on pollen micro-morphology, pollen storage methods, and cross-compatibility among grape (Vitis spp.) genotypes.

The knowledge of pollen morphology, suitable storage condition, and species compatibility is vital for a successful grapevine improvement programme. Ten grape genotypes from three different species, viz., Vitis vinifera L., Vitis parviflora Roxb., and Vitis champini Planc., were studied for their pollen structure and pollen storage with the objective of determining their utilization in grape rootstock improvement programs. Pollen morphology was examined through the use of a scanning electron microscope (SEM). The viability of the pollen was assessed using 2,3,5-triphenyltetrazolium chloride (TTC). In vitro pollen germination was investigated using the semi-solid medium with 10 % sucrose, 100 mg/L boric acid, and 300 mg/L calcium nitrate. The results revealed variations in pollen micro-morphology in 10 genotypes, with distinct pollen dimensions, shapes, and exine ornamentation. However, species-wise, no clear difference was found for these parameters. Pollen of V. parviflora Roxb. and Dogridge was acolporated and did not germinate. The remaining eight genotypes exhibited tricolporated pollen and showed satisfactory in vitro pollen germination. Storage temperature and duration interactions showed that, at room temperature, pollen of most of the grape genotypes can be stored for up to 1 day only with an acceptable pollen germination rate (>30 %). However, storage for up to 7 days was successfully achieved at 4 °C, except for 'Pearl of Csaba'. The most effective storage conditions were found to be at -20 °C and -196 °C (in liquid N2), enabling pollen storage for a period of up to 30 days, and can be used for pollination to overcome the challenge of asynchronous flowering. Four interspecific combinations were studied for their compatibility, among which V. parviflora Roxb. × V. vinifera L. (Pusa Navrang) and V. parviflora Roxb. × V. champini Planc. (Salt Creek) showed high cross-compatibility, offering their potential use for grape rootstock breeding. However, V. parviflora Roxb. × V. vinifera L. (Male Hybrid) recorded the lowest compatibility index among studied crosses. In the case of self-pollinated flowers from V. parviflora Roxb. and V. parviflora Roxb. × V. champini Planc. (Dogridge), pollen failed to germinate on the stigma due to male sterility caused by acolporated pollen. As a result, the flowers of these genotypes functioned as females, which means they are ideal female parents for grape breeding without the need for the tedious process of emasculation.

Discovery of Anti-NRLP3 Inflammasome, Immunomodulatory Phytochemicals from the Extract of Habenaria intermediaD. Don: An Unexplored Plant Species.

The present study describes the isolation, identification, and quantification of biomarker compounds in plant extracts of Habenaria intermedia D. Don (Orchidaceae). The isolation of the compounds was carried out from H. intermedia D. Don by repeated column chromatography of petroleum ether and ethanol fractions of extract of tubers. These compounds were characterized by 1H and 13C NMR and mass spectral data. A new quantitative method was established by using high-performance liquid chromatography (HPLC)-PDA. As a result, seven compounds were isolated and characterized. This is the first report of isolation of these compounds from this plant species H. intermedia D.Don. Out of seven isolated compounds, five were used for the quantitative study. A reliable and suitable HPLC method was developed for the well-resolved chromatogram of compounds. The proposed method was applied successfully to the detection and quantification of compounds. This study also represents the immunomodulatory and anti-inflammasome biological studies of isolated natural products. Loroglossol (HBR-4) has been reported to possess immunomodulatory activity. The immunostimulating assay indicated that HBR-4 could significantly promote the cell proliferation, especially via IL-2, TNF-α, and IFN-γ secretion from spleen cells. These results suggested the potential utilization of HBR-4 as an attractive functional health supplement candidate for hypoimmunity population. Additionally, cyclophosphamide-induced immunosuppression was counteracted by treatment with HBR-4, revealing significant increase in hemagglutinating antibody responses and hemolytic antibody responses. The current work revealed the potential anti-inflammasome and immunomodulatory activities of H. intermedia D. Don compounds and validates the usage of this prominent Rasayna plant.

Dereplication approach for the first time isolation of tatarinowin a and pentadecanoic acid from Acorus calamus L. by using GC-MS.

In the present study, we report herein the isolation of cadinane-type sesquiterpenoid, tatarinowin A (ACH-6), and pentadecanoic acid (ACH-8) from petroleum ether extract of rhizome of Acorus calamus L. (Acoraceae) along with 6 other known compounds in this species. It is pertinent to mention here that this is the first report to stain these compounds in which dereplication approach based on GC-MS was applied to target unknown compounds ACH-6 and ACH-8 in A. calamus L. Derelpication approaches based on GC-MS is very useful technique in the area of drug discovery and have eminence potential to identify known and unknown compounds present in extracts of medicinal important plants. This technique can be used to expedite the process of purification of unknown compounds from different matrixes. The isolated compounds were identified with the help of inbuilt library search which reveals the presence of 17 known and 4 unknown compounds. Further, the structure elucidation of all isolated compounds was done using spectroscopy techniques. Also, the structure of ACH-6 was further confirmed by using the single-crystal X-ray diffraction technique.

Assessing the genetic diversity of guava germplasm characterized by morpho-biochemical traits.

Amid environmental crises, a galloping population, and changing food habits, increasing fruit production with nutritional quality is a global challenge. To address this, there is a necessity to exploit the germplasm accessions in order to develop high-yielding varieties/hybrids with good adaptability and high quality fruit under changing environmental and biological conditions. In the study, a total of 33 morpho-biochemical traits enabled an assessment of the genetic variability, diversity, and structure in a collection of 28 diverse germplasm lines of guava. Results showed that highly significant genetic variability existed in the studied traits in the guava germplasm. The coefficient of variation values for the qualitative and quantitative traits varied from 23.5-72.36 to 1.39-58.62%, respectively. Germplasm Thai, Lucknow-49, Punjab Pink, Psidium friedrichsthalianum, and Shweta had the highest fruit weight (359.32 g), ascorbic acid content (197.27 mg/100 g fruit), total phenolic content (186.93 mg GAE/100 g), titratable acidity (0.69 percent), and antioxidant capacity (44.49 µmolTrolox/g), respectively. Fruit weight was positively correlated with ascorbic acid content; however, titratable acidity was negatively correlated with fruit weight. The principal component analysis (PCA) was 84.2% and 93.3% for qualitative and quantitative traits, respectively. Furthermore, K-mean clustering was executed; the population was grouped into three clusters for both traits. Additionally, the dendrogram using agglomerative hierarchical clustering (AHC), where all the germplasm were grouped into four clusters, revealed that among the clusters, clusters III and IV were highly divergent. The high variability, diversity, and structure could be utilized for the breeding programme of guava and also explored for molecular analysis using next-generation technology to enhance the guava yield and nutrition properties and also develop the climate resilient technology to fulfill the existing demand gap and nutrition availability, which could not only mitigate the nutrition requirement but also enhance the easy availability of fruits year-round.

Dereplication Based Strategy for Rapid Identification and Isolation of a Novel Anti-inflammatory Flavonoid by LCMS/MS from Colebrookea oppositifolia.

Colebrookea oppositifolia is a folkloric medicinal plant, well known for its tremendous medicinal properties such as curing epilepsy, ulcers, and urinary problems. The aim of the present study was to apply the dereplication strategy on the ethanol extract of C. oppositifolia with potent anti-inflammatory activity for the rapid identification and isolation of novel bioactive molecules to aid the drug discovery process. An integrated approach using liquid chromatography-mass spectrometry (LCMS) followed by preparative high-performance liquid chromatography (HPLC) was used for the isolation of potent molecules from the anti-inflammatory extract of C. oppositifolia . Purity of the compounds (>98.5%) was established by HPLC, and identification was carried out by NMR and ESI-MS. 5,6,7-Trihydroxyflavone-3-O-glucuronide methyl ester (compound III) isolated from C. oppositifolia was extensively studied for anti-inflammatory potential in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the mice model. Compound III significantly repressed various proinflammatory mediators and upregulated the release of anti-inflammatory cytokine IL-10. Compound III reduced inflammation when studied for parameters such as the phagocytic index, carrageenan-induced paw edema in mice, and effect on organ weight. It reduced inflammation in a dose-dependent manner both in vitro and in vivo. Further molecular insights into the study revealed that compound III blocks the phosphorylation of I kappa b kinase α/ß (IKKα/ß), IκBα, and nuclear factor kB p65 (NF-κBp65) which is a key controller of inflammation, thereby showing anti-inflammatory potential. Hence, this study permits further investigation to develop compound III as an anti-inflammatory drug.

COVID-19 vaccine hesitancy among medical students in India.

The coronavirus disease 2019 (COVID-19) vaccine was launched in India on 16 January 2021, prioritising health care workers which included medical students. We aimed to assess vaccine hesitancy and factors related to it among medical students in India. An online questionnaire was filled by 1068 medical students across 22 states and union territories of India from 2 February to 7 March 2021. Vaccine hesitancy was found among 10.6%. Concern regarding vaccine safety and efficacy, lack of awareness regarding their eligibility for vaccination and lack of trust in government agencies predicted COVID-19 vaccine hesitancy among medical students. On the other hand, the presence of risk perception regarding themselves being affected with COVID-19 reduced vaccine hesitancy as well as hesitancy in participating in COVID-19 vaccine trials. Vaccine-hesitant students were more likely to derive information from social media and less likely from teachers at their medical colleges. Choosing between the two available vaccines (Covishield and Covaxin) was considered important by medical students both for themselves and for their future patients. Covishield was preferred to Covaxin by students. Majority of those willing to take the COVID-19 vaccine felt that it was important for them to resume their clinical posting, face-to-face classes and get their personal life back on track. Around three-fourths medical students viewed that COVID-19 vaccine should be made mandatory for both health care workers and international travellers. Prior adult vaccination did not have an effect on COVID-19 vaccine hesitancy. Targeted awareness campaigns, regulatory oversight of vaccine trials and public release of safety and efficacy data and trust building activities could further reduce COVID-19 vaccine hesitancy among medical students.

Tobacco, alcohol use and other risk factors for developing symptomatic COVID-19 vs asymptomatic SARS-CoV-2 infection: a case-control study from western Rajasthan, India.

BACKGROUND: Understanding risk factors of symptomatic coronavirus disease 2019 (COVID-19) vis-à-vis asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severe disease and death is important. METHODS: An unmatched case-control study was conducted through telephonic interviews among individuals who tested positive for SARS-CoV-2 in Jodhpur, India from 23 March to 20 July 2020. Contact history, comorbidities and tobacco and alcohol use were elicited using standard tools. RESULTS: Among 911 SARS-CoV-2-infected individuals, 47.5% were symptomatic, 14.1% had severe COVID-19 and 41 (4.5%) died. Older age, working outside the home, cardiac and respiratory comorbidity and alcohol use were found to increase the risk of symptomatic disease as compared with asymptomatic infection. Current tobacco smoking (odds ratio [OR] 0.46 [95% confidence interval {CI} 0.26 to 0.78]) but not smokeless tobacco use (OR 0.81 [95% CI 0.55 to 1.19]) appeared to reduce the risk of symptomatic disease. Age ≥60 y and renal comorbidity were significantly associated with severe COVID-19. Age ≥60 y and respiratory and cardiac comorbidity were found to predispose to mortality. CONCLUSIONS: The apparent reduced risk of symptomatic COVID-19 among tobacco smokers could be due to residual confounding owing to unknown factors, while acknowledging the limitation of recall bias. Cross-protection afforded by frequent upper respiratory tract infection among tobacco smokers could explain why a similar association was not found for smokeless tobacco use, thereby being more plausible than the 'nicotinic hypothesis'. Those with comorbidities and age ≥60 y should be prioritized for hospital admission.

Investigating 11 Withanosides and Withanolides by UHPLC-PDA and Mass Fragmentation Studies from Ashwagandha (Withania somnifera).

Withania somnifera (WS), also known as ashwagandha or Indian ginseng, is known for its pharmacological significance in neurodegenerative diseases, stress, cancer, immunomodulatory, and antiviral activity. In this study, the WS extract (WSE) from the root was subjected to ultrahigh-performance liquid chromatography with photodiode array detection (UHPLC-PDA) analysis to separate 11 withanoside and withanolide compounds. The quantification validation was carried out as per ICHQ2R1 guidelines in a single methodology. The calibration curves were linear (r 2 > 0.99) for all 11 compounds within the tested concentration ranges. The limits of detection and quantification were in the range of 0.213-0.362 and 0.646-1.098 µg/mL, respectively. The results were precise (relative standard deviation, <5.0%) and accurate (relative error, 0.01-0.76). All compounds showed good recoveries of 84.77-100.11%. For the first time, withanoside VII, 27-hydroxywithanone, dihydrowithaferin A, and viscosalactone B were quantified and validated along with bioactive compounds withanoside IV, withanoside V, withaferin A, 12-deoxywithastramonolide, withanolide A, withanone, and withanolide B simultaneously in WS. This UHPLC-PDA method has practical adaptability for ashwagandha raw material, extract, and product manufacturers, along with basic and applied science researchers. The method has been developed on UHPLC for routine analysis. The 11 withanosides and withanolides were confirmed using the fragmentation pattern obtained by the combined use of electrospray ionization and collision-induced dissociation in triple-quadrupole tandem mass spectrometry (TQ-MS/MS) in the WSE.

Transmission Dynamics of the COVID-19 Epidemic at the District Level in India: Prospective Observational Study.

BACKGROUND: On March 9, 2020, the first COVID-19 case was reported in Jodhpur, Rajasthan, in the northwestern part of India. Understanding the epidemiology of COVID-19 at a local level is becoming increasingly important to guide measures to control the pandemic. OBJECTIVE: The aim of this study was to estimate the serial interval and basic reproduction number (R0) to understand the transmission dynamics of the COVID-19 outbreak at a district level. We used standard mathematical modeling approaches to assess the utility of these factors in determining the effectiveness of COVID-19 responses and projecting the size of the epidemic. METHODS: Contact tracing of individuals infected with SARS-CoV-2 was performed to obtain the serial intervals. The median and 95th percentile values of the SARS-CoV-2 serial interval were obtained from the best fits with the weibull, log-normal, log-logistic, gamma, and generalized gamma distributions. Aggregate and instantaneous R0 values were derived with different methods using the EarlyR and EpiEstim packages in R software. RESULTS: The median and 95th percentile values of the serial interval were 5.23 days (95% CI 4.72-5.79) and 13.20 days (95% CI 10.90-18.18), respectively. R0 during the first 30 days of the outbreak was 1.62 (95% CI 1.07-2.17), which subsequently decreased to 1.15 (95% CI 1.09-1.21). The peak instantaneous R0 values obtained using a Poisson process developed by Jombert et al were 6.53 (95% CI 2.12-13.38) and 3.43 (95% CI 1.71-5.74) for sliding time windows of 7 and 14 days, respectively. The peak R0 values obtained using the method by Wallinga and Teunis were 2.96 (95% CI 2.52-3.36) and 2.92 (95% CI 2.65-3.22) for sliding time windows of 7 and 14 days, respectively. R0 values of 1.21 (95% CI 1.09-1.34) and 1.12 (95% CI 1.03-1.21) for the 7- and 14-day sliding time windows, respectively, were obtained on July 6, 2020, using method by Jombert et al. Using the method by Wallinga and Teunis, values of 0.32 (95% CI 0.27-0.36) and 0.61 (95% CI 0.58-0.63) were obtained for the 7- and 14-day sliding time windows, respectively. The projection of cases over the next month was 2131 (95% CI 1799-2462). Reductions of transmission by 25% and 50% corresponding to reasonable and aggressive control measures could lead to 58.7% and 84.0% reductions in epidemic size, respectively. CONCLUSIONS: The projected transmission reductions indicate that strengthening control measures could lead to proportionate reductions of the size of the COVID-19 epidemic. Time-dependent instantaneous R0 estimation based on the process by Jombart et al was found to be better suited for guiding COVID-19 response at the district level than overall R0 or instantaneous R0 estimation by the Wallinga and Teunis method. A data-driven approach at the local level is proposed to be useful in guiding public health strategy and surge capacity planning.

MicroRNA hsa-miR-324-5p Suppresses H5N1 Virus Replication by Targeting the Viral PB1 and Host CUEDC2.

MicroRNAs (miRNAs) are small noncoding RNAs that are crucial posttranscriptional regulators for host mRNAs. Recent studies indicate that miRNAs may modulate host response during RNA virus infection. However, the role of miRNAs in immune response against H5N1 infection is not clearly understood. In this study, we showed that expression of cellular miRNA miR-324-5p was downregulated in A549 cells in response to infection with RNA viruses H5N1, A/PR8/H1N1, and Newcastle disease virus (NDV) and transfection with poly(I·C). We found that miR-324-5p inhibited H5N1 replication by targeting the PB1 viral RNA of H5N1 in host cells. In addition, transcriptome analysis revealed that miR-324-5p enhanced the expression of type I interferon, type III interferon, and interferon-inducible genes (ISGs) by targeting CUEDC2, the negative regulator of the JAK1-STAT3 pathway. Together, these findings highlight that the miR-324-5p plays a crucial role in host defense against H5N1 by targeting viral PB1 and host CUEDC2 to inhibit H5N1 replication.IMPORTANCE Highly pathogenic influenza A virus (HPAIV) continues to pose a pandemic threat globally. From 2003 to 2017, H5N1 HPAIV caused 453 human deaths, giving it a high mortality rate (52.74%). This work shows that miR-324-5p suppresses H5N1 HPAIV replication by directly targeting the viral genome (thereby inhibiting viral gene expression) and cellular CUEDC2 gene, the negative regulator of the interferon pathway (thereby enhancing antiviral genes). Our study enhances the knowledge of the role of microRNAs in the cellular response to viral infection. Also, the study provides help in understanding how the host cells utilize small RNAs in controlling the viral burden.

Paradigm shift - Metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery.

Fatty acid drug discovery (FADD) is defined as the identification of novel, specialized bioactive mediators that are derived from fatty acids and have precise pharmacological/therapeutic potential. A number of reports indicate that dietary intake of omega-3 fatty acids and limited intake of omega-6 promotes overall health benefits. In 1929, Burr and Burr indicated the significant role of essential fatty acids for survival and functional health of many organs. In reference to specific dietary benefits of differential omega-3 fatty acids, docosahexaenoic and eicosapentaenoic acids (DHA and EPA) are transformed to monohydroxy, dihydroxy, trihydroxy, and other complex mediators during infection, injury, and exercise to resolve inflammation. The presented FADD approach describes the metabolic transformation of DHA and EPA in response to injury, infection, and exercise to govern uncontrolled inflammation. Metabolic transformation of DHA and EPA into a number of pro-resolving molecules exemplifies a novel, inexpensive approach compared to traditional, expensive drug discovery. DHA and EPA have been recommended for prevention of cardiovascular disease since 1970. Therefore, the FADD approach is relevant to cardiovascular disease and resolution of inflammation in many injury models. Future research demands identification of novel action targets, receptors for biomolecules, mechanism(s), and drug-interactions with resolvins in order to maintain homeostasis.

Evaluation of therapeutic potential of the silver/silver chloride nanoparticles synthesized with the aqueous leaf extract of Rumex acetosa.

Silver nanoparticles were green synthesized with the aqueous leaf extract of the widely consumed green leafy vegetable, Rumex acetosa (sorrel) and the obtained silver nanoparticles (Ag NPs) were tested for their in vitro antioxidant potential, cytotoxicity against human osteosarcoma (HOS) cell lines and antibacterial effects against sixteen human pathogenic clinical isolates. Different analytical techniques viz. UV-vis, FTIR, XRD, SEM-EDX and TEM were employed to characterize the synthesized Ag NPs. Surface Plasmon spectra for the Ag NPs with brownish black color were centered approximately at 448 nm. FTIR analysis revealed the presence of reactive N-H and O-H groups that are effective in reducing Ag(I) ions to Ag(0) which then reacted with the contents of the extract to AgCl/Ag2C2O4. From SEM and TEM analyses, the particles were found to be predominantly spherical in shape and ranged in size from 5 nm to 80 nm, but were largely in the range of 15 nm to 20 nm. Ag NPs showed considerable antioxidant activity, and all the sixteen clinical isolates of human pathogens tested were significantly inhibited. Also, HOS cell lines were significantly (p < 0.05) inhibited at 25% concentration of the Ag NPs extract, while showing a marginal revival at 50% and 100% concentrations.

Broad substrate affinity and catalytic diversity of fibrinolytic enzyme from Pheretima posthumous-Purification and molecular characterization study.

In this research, a serine protease was isolated and purified from Indian earthworm Pheretima posthumous by fractionation with ammonium sulfate followed by ion exchange and size exclusion chromatography. The molecular weight of purified protease was determined 29.5kDa by Maldi-TOF/MS. The enzyme exhibited a maximum proteolytic activity of 1.2U/ml with specific activity of 17.65U/mg at pH 8 and temperature 40°C. 2D electrophoresis study illustrated purity of enzyme, purified as a single peptide and isoelectric point (pI) 4.5. The enzyme has shown tremendous stability and proteolytic activity in the wide range of pH range (4-12) and temperatures (20-60°C). The kinetic constant Km and Vmax of purified protease were reported 0.09mg/ml and 23.25mg/ml/min. The enzyme also possesses excellent catalytic capacity with Kcat (341.9min-1) and catalytic efficiency (3798.88). The N-terminal sequence of purified protease Arg-Lys-Lys-Gly-Ala-Ser-Try-Phe-Try-Pro-Trp-Ser-Val-Lys-Lys-Arg, PMF and MS/MS studies had shown a partial homology with Lumbrokinase-P2 (2) from Lumbricus rubellus. The CD spectroscopy result provided an evidence for broad substrate affinity and stability of enzyme. The different forms of secondary structures determined in EFE result broad substrate affinity of enzyme.

Enzyme promiscuity in earthworm serine protease: substrate versatility and therapeutic potential.

Enzymes are the most versatile molecules in the biological world. These amazing molecules play an integral role in the regulation of various metabolic pathways and physiology subsequently. Promiscuity of an enzyme is the capacity to catalyze additional biochemical reactions besides their native one. Catalytic promiscuity has shown great impact in enzyme engineering for commercial enzyme and therapeutics with natural or engineered catalytic promiscuity. The earthworm serine protease (ESP) is a classic example of enzyme promiscuity and studied for its therapeutic potential over the last few decades. The ESP was reported for several therapeutic properties and fibrinolytic activity has been much explored. ESP, a complex enzyme exists as several isoforms of molecular weight ranging from 14 to 33 kDa. The fibrinolytic capacity of the enzyme has been studied in different species of earthworm and molecular mechanism is quite different from conventional thrombolytics. Cytotoxic and anti-tumor activities of ESP were evaluated using several cancer cell lines. Enzyme had shown tremendous scope in fighting against plant viruses and microbes. ESP is also reported for anti-inflammatory activity and anti-oxidant property. Apart from these, recently, ESP is reported for DNase activity. The daunting challenge for researchers is to understand the molecular mechanism for such diverse properties and possibility of enzyme promiscuity. This review emphasizes molecular mechanism of ESP governing various biochemical reactions. Further, the concept of enzyme promiscuity in ESP towards development of novel enzyme based drugs has been reviewed in this study.

Understanding the major risk factors in the beginning and the progression of rheumatoid arthritis: current scenario and future prospects.

Rheumatoid arthritis (RA), a chronic progressive inflammatory autoimmune disorder characterized by chronic pain and swelling primarily, affects the peripheral joints. RA had attained global concern in the last few decades, affecting more than 1.5 % of the world's population with higher female percentage than male. In the advanced stage, the disease is associated with the destruction of cartilage and bone along with a variety of systemic manifestations leading to functional disability. Inadequate early/preliminary diagnosis and non-specific therapeutics are the major challenges in the management of RA. Till date, the exact cause(s) of the disease remain(s) obscure, and several genetic, hormonal, and environmental factors are associated with the beginning and the progression of the disease. Rheumatoid factor is the only clinically approved bio-marker for the diagnosis, and RA is not restricted to bones, but also affects several vital organs in the advanced stages. Genome-wide association studies have explored novel genetic loci underlying common autoimmune diseases including RA. Recent discoveries of risk alleles have made it possible to define genetic risk profiles of patients with RA. The conventional non-steroidal anti-inflammatory drugs and steroidal drugs are still the choice for the treatment of RA under acute and chronic pathological conditions respectively. However, disease-modifying anti-rheumatic drugs have shown remarkable success in the last decade. The present review provides a comprehensive understanding of the major risk factors and the molecular biology involved in the initiation and the progression of RA with a note on the recent trends in RA therapy.

Targeting therapeutics across the blood brain barrier (BBB), prerequisite towards thrombolytic therapy for cerebrovascular disorders-an overview and advancements.

Cerebral tissues possess highly selective and dynamic protection known as blood brain barrier (BBB) that regulates brain homeostasis and provides protection against invading pathogens and various chemicals including drug molecules. Such natural protection strictly monitors entry of drug molecules often required for the management of several diseases and disorders including cerebral vascular and neurological disorders. However, in recent times, the ischemic cerebrovascular disease and clinical manifestation of acute arterial thrombosis are the most common causes of mortality and morbidity worldwide. The management of cerebral Ischemia requires immediate infusion of external thrombolytic into systemic circulation and must cross the blood brain barrier. The major challenge with available thrombolytic is their poor affinity towards the blood brain barrier and cerebral tissue subsequently. In the clinical practice, a high dose of thrombolytic often prescribed to deliver drugs across the blood brain barrier which results in drug dependent toxicity leading to damage of neuronal tissues. In recent times, more emphasis was given to utilize blood brain barrier transport mechanism to deliver drugs in neuronal tissue. The blood brain barrier expresses a series of receptor on membrane became an ideal target for selective drug delivery. In this review, the author has given more emphasis molecular biology of receptor on blood brain barrier and their potential as a carrier for drug molecules to cerebral tissues. Further, the use of nanoscale design and real-time monitoring for developed therapeutic to encounter drug dependent toxicity has been reviewed in this study.