A leap towards enforcing medicines prescribing by generic names in low- and middle-income countries (LMICs): pitfalls, limitations, and recommendations for local drug regulatory agencies.

The Drug Regulatory Authority of Pakistan (DRAP) in response to the public outcry on increasing medicines prices in the country issued notifications to direct healthcare professionals to prescribe medicines with their generic names. Like DRAP, many regulators in the low- and middle-income countries (LMICs) are also inspiring from the west to legally enforce generic prescribing in a bid to reduce the out-of-pocket public expenditures. However, there are pitfalls in the LMICs drug regulatory framework, which if left unaddressed can severely jeopardise the foreseen benefits of medicines prescribing by generic names. This article critically appraises the impact of prescribing by generic names regulations in LMICs and highlights the key considerations that are vital to address before legally enforcing generic prescribing. The ethics, regulatory compliance, and good governance are the key to success; better generics for a better tomorrow.

A novel synthetic derivative of biaryl guanidine as a potential BACE1 inhibitor, to treat Alzheimer's disease: In-silico, in-vitro and in-vivo evaluation.

BACE1 enzyme has been known a potential target involved in Alzheimer's disease (AD). Present research was focused on the principles of virtually screening, chemical synthesis and protease inhibitory effect of BACE1 enzyme via biaryl guanidine derivatives. In-silico based paradigm (ligand binding interaction within active domain of BACE 1 enzyme i.e., aspartate Asp32 and Asp228) a novel compound was synthesized and subsequently subjected to in-vitro and in-vivo evaluation. 1,3-di(isoquinolin-6-yl) guanidine was synthesized and found potent (IC50 6±0.56 µM) and active to arrest (99 %) ß-secretase enzyme (FRET assay). Furthermore, it was found to improve novel object recognition test (RTI =56.55%) and Morris water maze test (32.26±3.45s) significantly (p<0.05). Enhanced pharmacokinetics and related properties (high iLOGP and Log S =-3.98) along with improved permeation to the blood brain barrier (BBB) (zero Lipinski violation) made it feasible to inhibit BACE1 as a novel therapeutic source to treat AD in future.

Identification of Heterotic Groups and Patterns Based on Genotypic and Phenotypic Characteristics Among Rice Accessions of Diverse Origins.

Identification of the right parental combinations to maximize heterosis is the major goal of hybrid breeding, which could be achieved through identification of heterotic groups. The main objective of this study was to identify promising heterotic groups for future rice breeding programs. A collection of 359 rice genotypes of diverse origins of China and abroad, composed of inbreds, maintainers, restorers, and temperature-sensitive genic male sterile (TGMS) lines were genotyped using 10K SNP chips. The SNP data set was subjected to genomic analyses for estimation of genetic divergence and diversity. Significant variations were observed in the germplasm with the identification of six different genetic groups. These lines were assigned to the genetic groups independent of their origin. Taking an account of commercially used heterotic groups present in each cluster, three cytoplasmic male sterile (CMS) lines and 14 inbred and restorer lines with moderate to high genetic distances selected from five heterotic patterns were crossed and obtained 42 F1 hybrids. A total of 14 hybrids were found with significant maximum mid- and better-parent heterosis, namely, TaifengA × Guang122, TaifengA × Wushansimiao, and TaifengA × Minghui63 for earliness; Guang8A × Huazhan for dwarf stature; and Guang8A × Huanghuzhan-1, TaifengA × Yuexiangzhan, Guang8A × Minhui3301, TianfengA × Guang122, Guang8A × Yahui2115, TianfengA × Huanghuazhan, TianfengA × Minghui63, TianfengA × Minhui3301, TaifengA × Gui99, and Guang8A × Yuenongsimiao for yield and yield-related traits. Mid-parent and better-parent heterotic F1 hybrids were in positive correlation with the genetic distances as that manifested by commercially used heterotic groups, encouraging the use of genotypic data for identification of heterotic groups. Our study provides an informative strategy for the development of early maturing, lodging resistant and high-yielding commercial hybrids and cultivars in future heterosis breeding programs.

Macro level influences on strategic responses to the COVID-19 pandemic - an international survey and tool for national assessments.

BACKGROUND: Variation in the approaches taken to contain the SARS-CoV-2 (COVID-19) pandemic at country level has been shaped by economic and political considerations, technical capacity, and assumptions about public behaviours. To address the limited application of learning from previous pandemics, this study aimed to analyse perceived facilitators and inhibitors during the pandemic and to inform the development of an assessment tool for pandemic response planning. METHODS: A cross-sectional electronic survey of health and non-health care professionals (5 May - 5 June 2020) in six languages, with respondents recruited via email, social media and website posting. Participants were asked to score inhibitors (-10 to 0) or facilitators (0 to +10) impacting country response to COVID-19 from the following domains - Political, Economic, Sociological, Technological, Ecological, Legislative, and wider Industry (the PESTELI framework). Participants were then asked to explain their responses using free text. Descriptive and thematic analysis was followed by triangulation with the literature and expert validation to develop the assessment tool, which was then compared with four existing pandemic planning frameworks. RESULTS: 928 respondents from 66 countries (57% health care professionals) participated. Political and economic influences were consistently perceived as powerful negative forces and technology as a facilitator across high- and low-income countries. The 103-item tool developed for guiding rapid situational assessment for pandemic planning is comprehensive when compared to existing tools and highlights the interconnectedness of the 7 domains. CONCLUSIONS: The tool developed and proposed addresses the problems associated with decision making in disciplinary silos and offers a means to refine future use of epidemic modelling.

Fabrication of Carbamazepine Cocrystals: Characterization, In Vitro and Comparative In Vivo Evaluation.

Carbamazepine (CBZ) is an antiepileptic drug having low bioavailability due to its hydrophobic nature. In the current study, efforts are made to investigate the effect of dicarboxylic acid coformer spacer groups (aliphatic chain length) on physicochemical properties, relative humidity (RH) stability, and oral bioavailability of CBZ cocrystals. Slurry crystallization technique was employed for the preparation of CBZ cocrystals with the following coformers: adipic (AA), glutaric (GA), succinic (SA), and malonic acid (MA). Powder X-ray diffractometry and Fourier-transform infrared spectroscopy confirmed cocrystal preparation. Physicochemical properties, RH stability, and oral bioavailability of cocrystals were investigated. Among the prepared cocrystals, CBZ-GA showed maximum solubility as well as improved dissolution profile (CBZ-GA > CBZ-MA > CBZ-AA > pure CBZ > CBZ-SA) in ethanol. Maximum RH stability was shown by CBZ-AA, CBZ-SA, and CBZ-MA. In vivo studies confirmed boosted oral bioavailability of cocrystals compared to pure CBZ. Furthermore, in vivo studies depicted the oral bioavailability order of cocrystals as CBZ-GA > CBZ-MA > Tegral® > CBZ-AA > CBZ-SA > pure CBZ. Thus, pharmaceutical scientists can effectively employ cocrystallization technique for tuning physicochemical properties of hydrophobic drugs to achieve the desired oral bioavailability. Overall, results reflect no consistent effect of spacer group on physicochemical properties, RH stability, and oral bioavailability of cocrystals.

Partial substitution of organic nitrogen with synthetic nitrogen enhances rice yield, grain starch metabolism and related genes expression under the dual cropping system.

Improving grain filling in the presernt farming systems is crucial where grain filling is a concern due to the extreme use of chemical fertilizers (CF). A field experiment was conducted at the experimental station of Guangxi University, China in 2019 to test the hypothesis that cattle manure (CM) and poultry manure (PM) combined with CF could improve rice grain filling rate, yield, biochemical and qualitative attributes. A total of six treatments, i.e., no fertilizer (T1), 100% CF (T2), 60% CM + 40% CF (T3), 30% CM + 70% CF (T4), 60% PM + 40% CF (T5), and 30% PM + 70% CF (T6) were used in this study. Results showed that the combined treatment T6increased starch metabolizing enzymes activity (SMEs), such as ADP-glucose phosphorylase (ADGPase) by 8 and 12%, soluble starch synthase (SSS) by 7 and 10%, granule bound starch synthesis (GBSS) by 7 and 9%, and starch branching enzyme (SBE) by 14 and 21% in the early and late seasons, respectively, compared with T2. Similarly, higher rice grain yield, grain filling rate, starch, and amylose content were also recorded in combined treatments. In terms of seasons, higher activity of SMEs , grain starch, and amylose content was noted in the late-season compared to the early season. The increment in these traits was mainly attributed to a lower temperature in the late season during the grain filling period. Furthermore, our results suggested that an increment in starch accumulation and grain filling rate were mainly associated with the enhanced sink capacity by regulating key enzyme activities involved in Suc-to-starch conversion. In-addition, RT-qPCR analysis showed higher expression levels of AGPS2b, SSS1, GBSS1, and GBSE11b genes, which resultantly increased the activities of SMEs during the grain filling period under combined treatments. Linear regression analysis revealed that the activity of ADGPase, SSS, GBSS, and SBE were highly positively correlated with starch and amylose accumulation. Thus, we concluded that a combination of 30% N from PM or CM with 70% N from CF is a promising option in terms of improving rice grain yield and quality. Our study provides a sustainable fertilizer management strategy to enhance rice grain yield and quality at the lowest environmental cost.

Smash ridge tillage strongly influence soil functionality, physiology and rice yield.

The practice of smash-ridging on dry land crop cultivation has shown much promise. However, the mechanism how does soil functionality and root traits can affect rice yield under smash ridge tillage with reduced nitrogen fertilization have not yet been explored. To fill this knowledge gap, we used three tillage methods-smash-ridging 40 cm (S40), smash-ridging 20 cm (S20), and traditional turn-over plowing 20 cm (T)-and two rice varieties (hybrid rice and conventional rice) and measured soil quality, root traits, rice yield and their correlation analysis at different growth stages. Soil physical and chemical properties were significantly improved by smash-ridging, including improvements in root morphological and physiological traits during three growth stages compared with T. S40 had the highest leaf area index (LAI), plant height (PH), and biomass accumulation (BA). Increment in biomass and panicle number (PN) resulted in higher grain yield (GY) of 6.9-9.4% compared with T. Correlation analysis revealed that root total absorption area (RTAA), root active absorption area (RAA), and root area ratio (RAR) were strongly correlated with soil quality. Root injury flow (RIF) and root biomass accumulation (RBA) were strongly correlated with LAI and above-ground plant biomass accumulation (AGBA). Conclusively, S40 is a promising option for improving soil quality, root traits, and consequently GY.

Investigating connections between COVID-19 pandemic, air pollution and community interventions for Pakistan employing geoinformation technologies.

Several major cities that witnessed heavy air pollution by particulate matter (PM2.5) concentration and nitrogen dioxide (NO2) have contributed to high rate of infection and severity of the coronavirus disease (COVID-19) pandemic. Owing to the negative impact of COVID-19 on health and economy, it is imperative to predict the pandemic trend of the COVID-19 outbreak. Pakistan is one of the mostly affected countries by recent COVID-19 pandemic in terms of COVID-cases and economic crises. Like other several Asian countries to combat the virus impacts, Pakistan implemented non-pharmacological interventions (NPI), such as national lockdowns. The current study investigates the effect of major interventions across three out of four provinces of Pakistan for the period from the start of the COVID-19 in March 22, 2020 until June 30, 2020, when lockdowns were started to be eased. High-resolution data on NO2 was recorded from Sentinel-5's Precursor spacecraft with TROPOspheric Monitoring Instrument (Sentinel-5P TROPOMI). Similarly, PM2.5 data were collected from sampling sties to investigate possible correlation among these pollutants and COVID-19. In addition, growth and susceptible-infected-recovered (SIR) models utilizing time-series data of COVID-19 from February 26 to December 31, 2020, with- and without NPI that encompass the predicted number of infected cases, peak time, impact on the healthcare system and mortality in Pakistan. Maximum mean PM2.5 concentration of 108 µgm-3 was recorded for Lahore with the range from 51 to 215 µgm-3, during strict lockdown (L), condition. This is three times higher than Pak-EPA and US-EPA and four times for WHO guidelines, followed by Peshawar (97.2 and 58 ± 130), Islamabad (83 and 158 ± 58), and Karachi (78 and 50 ± 140). The majority of sampling sites in Lahore showed NO2 levels higher than 8.75E-5 (mol/m2) in 2020 compared to 2019 during "L" period. The susceptible-infected-recovered (SIR) model depicted a strong correlation (r) between the predicted and reported cases for Punjab (r = 0.79), Sindh (r = 0.91), Khyber Pakhtunkhwa (KPK) (r = 94) and Islamabad (r = 0.85). Findings showed that major NPI and lockdowns especially have had a large effect on minimizing transmission. Continued community intervention should be undertaken to keep transmission of SARS-CoV-2 under control in cities where higher incidence of COVID-19 cases until the vaccine is available. This study provides a methodological framework that if adopted can assist epidemiologist and policy makers to be well-prepared in advance in cities where PM2.5 concentration and NO2 levels are already high in order to minimize the potential risk of further spread of COVID-19 cases.

Multivariate analysis for various quantitative traits in wheat advanced lines.

Genetic diversity play key role in the germplasm improvement which is directly correlated with the crop production. Various statistical techniques have been used to study diversity among different genotypes. Among these techniques multivariate is most frequently used one for the genetic association of genotypes. In the present study a total of 64 advance lines included one check cultivar were evaluated under the field conditions of Cereal Crop Research Institute, Pirsabaq Nowshera, Pakistan during September 2017. Data were recorded for nine different parameters. Multivariate analysis divided the total 64 genotypes into four groups. The first five PCs with Eigen values > 1 contributed 86.95% of the variability amongst genotypes. Characters with maximum values in PC1 were Spikelets spike-1 (SPPS) (0.732), spike length (SPL) (0.722) and biological yield (BY) (0.607), PC2 comprised of 100-grain weight (TGW) (0.605), grain yield (GY) (0.482) while days to heading (DH) (0.393), for PC3 major contributors were BY (0.550) and number of tillers meter square-1 (NTPS) (0.289), the contribution of PC4 were flag leaf area (FLA) (0.716) and SPL (0.298) and the maximum values for various traits in PC5 were SPPS (0.732), SPL (0.722) and BY (0.607). From the findings of present study best performing lines can be directly recommended for general cultivation or to be used in future breeding programs.

Synthesis, in-vitro, in-vivo anti-inflammatory activities and molecular docking studies of acyl and salicylic acid hydrazide derivatives.

Over the course of time several drugs have been synthesized and are available in market for the treatment of inflammation. However, they were unable to cure effectively and associated with side effects. To effectively deal with such diseases, heterocycles and their derivatives have gained their special position. For this reason 1,3,4-oxadiazole (15-16), 1,2,4-triazole (17-18), Schiff base (19-24) and 3,5-disubstituted pyrazole (25) derivatives were synthesized starting from salicylic acid and acyl acid hydrazides (12-14) as COX-1 and COX-2 inhibitors. In vivo anti-inflammatory activities were also tested by carrageenan-induced mice paw edema against albino mice of any sex. Structures of all the synthesized compounds were confirmed by FT-IR and 1H NMR analysis. Schiff base derivative of 4-amiontirazole (24) with IC50 value of 1.76 ± 0.05 (COX-2) and 117.8 ± 2.59 emerged as potent COX-2 inhibitor. Furthermore, we also performed in-vivo anti-inflammatory investigations by using carrageenan induced paw edema test. From in-vivo anti-inflammatory activities, it was found that after 1 h the maximum percentage inhibition 15.8% was observed by compound 14 which is comparable with that of the standard drug followed by the compound 18 with percentage inhibition of 10.5%. After 3 h, the maximum percentage inhibition was observed by compound 18 with 22.2% and compound 14 with 16.7%. After 5 h the maximum percentage inhibition was observed by compound 18 with 29.4% followed by compound 16 with 23.5%. We further explore the mechanism of the inhibition by using docking simulations. Docking studies revealed that the selective COX-2 inhibitors established interactions with additional COX-2 enzyme pocket residues.

Erratic Behavioral Attitude Leads to Noncommunicable Diseases: A Cross-Sectional Study.

BACKGROUND: The burden of noncommunicable diseases (NCDs) in the Arab world has reached an alarming level. Behavioral risk factors including consumption of fast food, inadequate sleep, and skipping meals are pervasive. This study aims at establishing the association between NCDs and modernized behavioral risk factors among populations. METHODS: A cross-sectional study was carried out with 1070 respondents who were 18 years old. The data were collected using a structured questionnaire with the help of the WHO STEPS approach with some modifications regarding NCD risk factors. RESULTS: 30% of respondents had cardiovascular diseases (CVD) followed by respiratory diseases (23%) and diabetes (3%) while the habit of smoking was found among 52% of respondents followed by physical inactivity (49%), skipping meals (24%), and inadequate sleep (30%). Consumption of fast food was found to be a significant risk factor for obesity (odds ratio (OR) = 2.72, 95% confidence interval (CI) [1.50, 4.92]), CVD (OR = 1.52, 95% CI [1.20, 1.94]), and respiratory disease (OR = 2.13, 95% CI [1.58, 2.86]). Significant linkages were found between CVD and smoking (OR = 0.69, 95% CI [0.54, 0.88]), diet pattern (OR = 1.86, 95% CI [1.44, 2.39]), fast food (OR = 1.52, 95% CI [1.20, 1.94]), and sleep hours (OR = 0.57, 95% CI [0.42, 0.79]). CONCLUSIONS: Undesirable behavioral risk factors pose a considerable threat to public health with a high prevalence rate of NCDs. Reducing the NCD burden and promoting healthy lifestyle formation of suitable strategies and their smooth implementation is the need of the hour.

Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to Arrest ß-Secretase Enzymatic Activity Involved in Alzheimer's Disease.

Proteases BACE1 (ß-secretases) enzymes have been recognized as a promising target associated with Alzheimer's disease (AD). This study was carried out on the principles of molecular docking, chemical synthesis, and enzymatic inhibition of BACE1 enzymes via biaryl guanidine-based ligands. Based on virtual screening, thirteen different compounds were synthesized and subsequently evaluated via in vitro and in vivo studies. Among them, 1,3-bis(5,6-difluoropyridin-3-yl)guanidine (compound (9)) was found the most potent (IC50 = 97 ± 0.91 nM) and active to arrest (99%) ß-secretase enzymes (FRET assay). Furthermore, it was found to improve the novel object recognition test and Morris water maze test significantly (p < 0.05). Improved pharmacokinetic parameters, viz., Log P o/w (1.76), Log S (-2.73), and better penetration to the brain (BBB permeation) with zero Lipinski violation, made it possible to hit the BACE1 as a potential therapeutic source for AD.

Effect of varying quantities of polymer on preparation and stability evaluation of carbamazepine cocrystals with dicarboxylic acid coformers.

The current study is an attempt to explore the effect of varying quantities of hydroxypropyl cellulose (HPC) polymer on carbamazepine (CBZ) cocrystal formation with dicarboxylic acid coformers i.e., malonic acid (MA), succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The cocrystals were first prepared without polymer by slurry crystallization method and then tried with different quantities of the polymer. The prepared samples were characterized by Powder X-ray Diffraction (XRPD). The characterization results indicate that in methanol pure carbamazepine-malonic (CBZ-MA) and carbamazepine-adipic acid (CBZ-AA) cocrystal can be prepared, while in ethanol and acetone pure carbamazepine-succinic (CBZ-SA) and carbamazepine-glutaric acid (CBZ-GA) cocrystals can be obtained respectively. The same cocrystals were tried using HPC polymer in three different quantities. The characterization results showed that a higher quantity of HPC polymer transforms CBZ-MA cocrystal polymorph-I to polymorph-II. The CBZ-SA and CBZ-GA cocrystal formation somehow inhibited as the concentration of HPC polymer increases. But on the other side, the formation of CBZ-AA cocrystal utterly not inhibited in the presence of varying quantities of HPC polymer. Furthermore, 11 different quantities of HPC were tried to know about the inhibitory concentration of HPC on CBZ-AA cocrystal formation. The CBZ-AA cocrystal preparation was not inhibited even at higher quantities of HPC compared to the coformer. Additionally, the effect of three different quantities of HPC on the thermal stability of the CBZ-AA cocrystal was investigated. Moreover, the stability of pure CBZ at 92% relative humidity (RH) condition was compared to CBZ-AA cocrystal with and without HPC polymer. The CBZ-AA cocrystal with and without HPC polymer was more stable than pure CBZ.

Erupt of malaria, dengue and chikungunya in Pakistan: Recent insights about prevalence, diagnosis and treatment.

Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in Pakistan. They pose a serious threat and cause a havoc for the victims owing to the life threatening signs and symptoms marked with elevated morbidity and mortality rate. It seems hard to discriminate due to common indications, consequently, deserves appropriate diagnosis prior elevated toll of death. Present article encompasses depth insights about their prevalence, diagnosis and clinical manifestation if erupt in the pandemic. However, host-vector-host cycle is the root cause of transmission and diverse mosquito species confer dissimilar infections. Indeed these infections are seasonal but other factors like flood, open irrigation channels, immense agricultural land, rich fauna and water reservoirs can't be overlooked. Dire need was felt to acknowledge and aware the public about local transmission, vector control, entomologic, research resources, diagnosis and advancement in healthcare system to alleviate them absolutely in future.

Understanding impact of pre-dissolved polymers on dissolution behavior of soluble carbamazepine cocrystal.

Cocrystallization is a novel approach for tackling the lower solubility concerns when they can yield solution concentration a lot better than their corresponding parent drug in crystalline form. To get the actual solubility and dissolution gains offered by the cocrystals, phase changes in solution (dissolution) has to be interrupted. In current study, we selected commonly used polymers in order to study their effects on the super saturation of carbamezepine-succinic acid (CBZ-SUC) cocrystal during dissolution studies. To observe solid phase changes during dissolution in situ Raman spectroscopy was used. At the completion of each test the solid phase was analyzed by Fourier-transform infrared spectroscopy (FTIR) and powder X-Ray diffractometry. In polymers absence, no dissolution improvement was achieved by the cocrystal owing to its quick transformation to the stable carbamazepine dihydrate (CBZDH). Pre-dissolved PVP at 2% w/v concentration did not inhibit CBZ crystallization as a dihydrate, whereas at 0.025% w/v pre-dissolved hydroxypropyl methyl cellulose acetate succinate (HPMCAS) did stabilize the cocrystal in buffer solution (pH 6.8) for the course of time studied. This cocrystal stabilization resulted in enhanced CBZ solubility ( Ì´ 4fold) caused by cocrystal super saturation state. Seeding of this stable supersaturated state with 1% w/v CBZDH resulted in CBZ crystallization as dihydrate with ultimate loss of solubility advantage.

Investigation of potent inhibitors of cholinesterase based on thiourea and pyrazoline derivatives: Synthesis, inhibition assay and molecular modeling studies.

Owing to the desperate need of new drugs development to treat Alzheimer's ailment the synthesis of 1-aroyl-3-(5-(4-chlorophenyl)-1,2,4-triazole-3-thioneaminylthioureas (2-6) starting from (4-amino-5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thiol) (1) and synthesis of 1-(3-(4-aminophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-2-(4-isobutylphenyl)propan-1-one (7-9) starting from 2-(4-isobutylphenyl)propanehydrazide (a) with the cyclization with substituted chalcones (c-e) was carried out. To check the biological potential of the synthesized compounds, all were subjected to acetylcholinesterase (AChE) and butrylcholinesterase (BChE) inhibition assays. The most potent and selective inhibitor for the acetylcholinesterase was compound 7 having an inhibitory concentration of 123 ±â€¯51 nM, whereas, compound 6 was found as selective inhibitor of butyrylcholinesterase (BChE) with an IC50 value of 201 ±â€¯80 nM. However, the compounds 1 and 2 were found as dual inhibitors i.e. active against both acetylcholinesterase as well as butyrylcholinesterase.

The wound healing and antibacterial potential of triple-component nanocomposite (chitosan-silver-sericin) films loaded with moxifloxacin.

AIM: The current study reports the development and evaluation of chitosan-sericin-silver nanocomposite (CSSN) films without and with moxifloxacin (Mox). METHODOLOGY: The film preparation method involved the in-situ synthesis of silver nanoparticles within the chitosan-sericin colloidal composite followed by preparation into a film by solvent casting technique. In-situ formation and the particle size analysis of the silver nanoparticles was performed via UV-Visible and zeta-size spectrometer. The prepared films were tested for swelling ratio, contents uniformity, in-vitro Mox release, and permeation analysis. The morphological (SEM), elemental (EDX), spectral (FT-IR), structural (XRD), and thermal (TGA and DSC) properties of the composites were also inspected. The antibacterial activity of the CSSN films was performed against seven pathogenic bacterial strains including five ATCC and two clinical strains. The potential wound healing activity of the composite films was evaluated on burn wound model induced in Sprague Dawley male rats. RESULTS: The prepared films displayed good swelling profile with a sustained in-vitro Mox release and permeation profile; attaining maximum of 78.57% (CSSM3) release and 55.05% (CSSM1) permeation (CSSM1) in 24 h. The prepared films, particularly the Mox-loaded CSSN films displayed a promising antibacterial activity against all the tested strains with the activity being highest against MRSA (clinical isolates). The prepared films indicated a remarkable wound healing applications with successful fibrosis, collagen reorganization, neovascularization, and mild epidermal regeneration after 7 days of treatment with no silver ions detection in animal's blood. CONCLUSION: The obtained findings strongly suggest the use of the prepared novel composite dressing for wound care applications.

Recent Progress in the Therapeutic Role of Serelaxin in Vascular Dysfunction.

Cardiovascular (CV) diseases are caused by vascular dysfunction. The enhanced sensitivity to vasoconstrictors, reduced endothelium-derived vasodilators nitric oxide (NO) and prostacyclin (PGI2), and endothelium-derived hyperpolarization (EDH) indicate CV dysfunction. In recent years, recombinant human relaxin, known as serelaxin, has emerged as a new vasoactive drug that is useful in acute heart failure. First part of this review article encompasses the role of endogenous relaxin in CV homeostasis. Subsequently, vascular effects of serelaxin and the underlying modes of action in comparison to other vasodilators are discussed. Finally, the usefulness of treatment with serelaxin in vascular dysfunction in different CV diseases, particularly due to oxidative stress, is explained.

Prioritizing and modelling of putative drug target proteins of Candida albicans by systems biology approach.

Candida albicans (Candida albicans) is one of the major sources of nosocomial infections in humans which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to treat affectively due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring 5090 completely annotated genes of Candida albicans from available databases which were categorized into essential and non-essential genes. The result indicated that 9% of proteins were essential and could become potential candidates for intervention which might result in pathogen eradication. We studied cluster of orthologs and the subtractive genomic analysis of these essential proteins against human genome was made as a reference to minimize the side effects. It was seen that 14% of Candida albicans proteins were evolutionary related to the human proteins while 86% are non-human homologs. In the next step of compatible drug target selections, the non-human homologs were sequentially compared to the human microbiome data to minimize the potential effects against gut flora which accumulated to 38% of the essential genome. The sub-cellular localization of these candidate proteins in fungal cellular systems indicated that 80% of them are cytoplasmic, 10% are mitochondrial and the remaining 10% are associated with the cell wall. The role of these non-human and non-gut flora putative target proteins in Candida albicans biological pathways was studied. Due to their integrated and critical role in Candida albicans replication cycle, four proteins were selected for molecular modeling. For drug designing and development, four high quality and reliable protein models with more than 70% sequence identity were constructed. These proteins are used for the docking studies of the known and new ligands (unpublished data). Our study will be an effective framework for drug target identifications of pathogenic microbial strains and development of new therapies against the infections they cause.