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Infectious pathologic changes caused by pathogens, which are harmful that enter the body by bacteria, fungus, viruses, and parasites. Infectious-diseases can range in severity from very mild to very dangerous. Numerous human diseases are caused by bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris and Bacillus subtilis. Capparis spp. that have anti-bacterial, anti-oxidant and anti-inflammatory properties, including spermidine, carotenoids, quercetin, tocopherol, and rutin by the anti-bacterial, anti-fungal, and anti-leishmanial action. Carrot seed oil (Daucus carota) and tea tree oil (Melaleuca alternifolia) both exhibit antibacterial action respectively. Curcumin and its derivatives were found to have more potent anti-bacterial activity against several strains of S. pneumonia. Oregano oil and carvacrol has revealed that they have anti-viral properties against respiratory-syncytial-virus (RSV), that causes respiratory disease, rotavirus, a frequent condition of diarrhea in theng children, and herpes simplex virus type 1 (HSV-1). Sweet basil extract, which contain ingredients like ursolic acid and apigenin, have powerful antiviral properties against hepatitis B, herpes and enterovirus. Candida infections have fewer severe side effects and less cost load than chemical medications, can be treated with new pharmaceuticals, plant, and herbal items.

Over the past decade, three-dimensional printing (3DP) has gained popularity among the public and the scientific community in a variety of disciplines, including engineering, medicine, manufacturing arts, and, more recently, education. The advantage of this technology is that it is capable of designing and printing almost any object shape using various materials such as ceramics, polymers, metals and bio.inks. This has further favored the use of this technology for biomedical applications in both clinical and research settings. In biomedicine, there has been a remarkable development of a variety of biomaterials, which in turn has accelerated the significant role of this technology as synthetic scaffolds in various forms such as scaffolds, constructs or matrices. In this chapter, we would like to review the trailblazing literature on the application of 3DP technology in biomedical engineering. This chapter focuses on various 3DP techniques and biomaterials for tissue engineering applications (TE). 3DP technology has a variety of applications in biomedicine and TE (B- TE). Customized structures for B- TE applications using 3DP have several advantages, e.g., they are easy to fabricate and are inexpensive. On the other hand, conventional technologies, which are costly, time-consuming, and labor intensive, are generally not compatible with 3DP. Therefore, the capabilities of 3DP, which is a novel fabrication technology, need to be explored for many other potential applications. Here, we provide a comprehensive overview of the different types of 3DP technologies and how they can potentially be used.

Mesenchymal stem cells (MSCs) are known for their multilineage differentiation potential with immune-modulatory properties. The molecular underpinnings of differentiation remain largely undefined. In this study, we investigated the cellular and molecular features of chemically induced osteogenesis from MSC isolated from human adipose tissue (human adipose MSCs, hAMSCs) using single-cell RNA-sequencing (scRNA-seq). We found that a near complete differentiation of osteogenic clusters from hAMSCs under a directional induction. Both groups of cells are heterogeneous, and some of the hAMSCs cells are intrinsically prepared for osteogenesis, while variant OS clusters seems in cooperation with a due division of the general function. We identified a set of genes related to cell stress response highly expressed during the differentiation. We also characterized a series of transitional transcriptional waves throughout the process from hAMSCs to osteoblast and specified the unique gene networks and epigenetic status as key markers of osteogenesis.

Clostridium botulinum is Gram-positive anaerobic spore-forming bacterium that produces very potent neurotoxins that have a potential to be used as bioweapon. In this study, we utilized applications of pan genome to develop drug targets for 51 strains of Clostridium botulinum. From the total 8756 core proteins, there were 422 non-host homologous proteins from which we selected 7 essential proteins by applying 2 thresholds that are identity > 35 and e-value = 0.001. These 7 proteins were selected as drug targets and docked against 105 anti-bacterial compounds. After docking, against each protein, top 10 compounds were selected based on the binding affinity and number of interactions and from these 10 compounds, the most promising compound was ranked on top for all target proteins. Furthermore, we also identified some compounds that have shown highest binding energies with more than one protein. From the 105 anti-bacterial compounds, we got 39 compounds on the basis of their binding energies with all target proteins. These compounds can be further validated by in vitro analysis and can proceed for clinical trials.

The study determines the prevalence and resistance among pathogenic bacteria against used antibiotics. The isolates were identified biochemically and subjected to antibiotic sensitivity using disk-diffusion method. A total of 210 bacterial isolates were tested, 175 (83.3%) were reported positive whereas 35 (16.6%) were found negative for HVS. The isolates were initially identified on colonies morphology and later via biochemical tests. The gram positive bacteria isolates i,e Staphylococcus aureus was found 48 (23.3%), followed by lactobacillus and least value belonged to Staphylococcus epidermidis i.e, 7 (3.3%). While gram negative bacteria Escherichia coli were 56 (26.6%), followed by Pseudomonas aeruginosa 36 (17.14%) and least value was of Proteus vulgaris. i.e, 7 (3.3%). All the isolates were subjected to antibiotics susceptibility testing. At least six antibiotics were shown to be resistant in bacterial isolates. Antibiotic resistance was found in considerable abundance in the clinical isolates, according to the findings. Antibiotic susceptibility testing and surveillance are essential on a regular basis to avoid treatment failure and the emergence of antibiotic resistance.

Introduction: Portal hypertensive gastropathy is a term applied to the typical appearance of the mucosa of stomach consisting of a mosaic-like diffuse and reticular cobblestone pattern of gastric mucosal layer secondary to increased blood pressure in the portal vein. Objective: To determine the occurrence and characteristic of portal hypertensive gastropathy in patients with liver cirrhosis Methodology: This study was descriptive cross-sectional piloted at the department of Medicine, Hayatabad medical complex Peshawar for duration of six months from November 2020 to May 2021. A total of 158 patients were observed in our study. All the data was entered and analyzed in SPSS version 21. Results: In our study portal Hypertensive Gastropathy was observed in 34(21.5%) cirrhosis patients while it was not observed in 124(78.5%) patients. Based on the class of portal hypertensive gastropathy, severe and mild types were observed in 43(27.2%) and 115(72.8%) patients respectively. Conclusion: In our study portal hypertensive gastropathy was observed in 34(21.5%) cirrhotic patients, amongst these 27.2% were severe and 72.8% were mild types. In cirrhotic and portal hypertensive gastropathy patients, these findings might have major therapeutic implications. Keywords: Frequency; Portal Hypertensive Gastropathy, Liver cirrhosis

Objective: Diabetes is one of the major risk factor responsible for poor outcomes of corona virus disease (COVID-19). Association between pre infection HbA1c level in diabetic individuals and severity of COVID-19 based on the requirement for hospitalization, will be helpful in controlling and defeating COVID-19. Methods: This was cross sectional study carried out in Khalifa Gul Nawaz, (KGN) hospital, Bannu, Pakistan. 160 diabetic individuals with COVID-19 were registered in this study. All the registered subjects were divided into Hospitalized COVID-19 Daibetic, (HCD group) and Non Hospitalized COVID-19 Daibetic (NHCD groups). In HCD group 32 diabetic individual with a deadly disease and severe complications of COVID-19 were considered while in NHCD group 128 diabetic individuals with mild complications of COVID-19 were present. Data analysis was performed by using IBM SPSS version 26. Results: Mean age of HCD group was significantly higher (p< 0.05) as compared to NHCD group. Among the different co-morbidities hypertension and chronic kidney diseases were significantly associated with hospitalization of COVID-19 individuals. But, after adjusting for several preexisting clinical factors, HbA1c ≥9% was the only predictor linked with a substantially higher risk of hospitalization in a multivariate analysis. Conclusion: Higher pre infection levels of HbA1c are clear markers for the hospitalization of COVID-19. Using HbA1c levels ≥ 9, we can highlight the high risk population and can successfully control and defeat COVID-19. Key words: Corona virus infectious disease 2019, Hospitalization, HbA1c, diabetes.

DFT calculations are carried out to investigate nonlinear optical (NLO) properties of superhalogen (BCl4) and superalkali (NLi4) doped graphitic carbon nitride (GCN). It is noted that the geometries of doped GCN are sufficiently stable. The energy gap for GCN is 3.89 and it reduces to 0.53 eV in our designed molecule G4. Change in the dipole and transition dipole moment is observed along with small transition energies which are responsible for higher hyperpolarizabilities. Doped GCN has larger first and second hyperpolarizabilities which are basic requirements for NLO response. The second hyperpolarizability of GCN enhances from 1.59 × 104 to 2.53 × 108 au when doping with BCl4 and NLi4. TD-DFT calculations show the absorption maxima of doped GCN range from 700 nm to 1350 nm. EDDM analysis provides information on electronic distribution from excited to ground state. All these consequences show doped GCN can be a promising NLO material.

The behavioural effects elicited by chemical constituents of Cannabis sativa, such as cannabidiol (CBD), on the ventromedial hypothalamus (VMH) are not well understood. There is evidence that VMH neurons play a relevant role in the modulation of unconditioned fear-related defensive behavioural reactions displayed by laboratory animals. This study was designed to explore the specific pattern of distribution of the CB1 receptors in the VMH and to investigate the role played by this cannabinoid receptor in the effect of CBD on the control of defensive behaviours and unconditioned fear-induced antinociception. A panic attack-like state was triggered in Wistar rats by intra-VMH microinjections of N-methyl-d-aspartate (NMDA). One of three different doses of CBD was microinjected into the VMH prior to local administration of NMDA. In addition, the most effective dose of CBD was used after pre-treatment with the CB1 receptor selective antagonist AM251, followed by NMDA microinjections in the VMH. The morphological procedures demonstrated distribution of labelled CB1 receptors on neuronal perikarya situated in dorsomedial, central and ventrolateral divisions of the VMH. The neuropharmacological approaches showed that both panic attack-like behaviours and unconditioned fear-induced antinociception decreased after intra-hypothalamic microinjections of CBD at the highest dose (100 nmol). These effects, however, were blocked by the administration of the CB1 receptor antagonist AM251 (100 pmol) in the VMH. These findings suggest that CBD causes panicolytic-like effects and reduces unconditioned fear-induced antinociception when administered in the VMH, and these effects are mediated by the CB1 receptor-endocannabinoid signalling mechanism in VMH.

The goal was to simply and efficiently predict the indicators of disease severity in knee osteoarthritis (KOA) patients.One hundred eighty-four patients with KOA and 126 healthy subjects were included. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was used as a reference index for disease severity in KOA patients, in which WOMAC80 was classified as mild and WOMAC ≥ 80 as moderate and severe. Blood routine parameters of the KOA and the healthy groups were analyzed by the Mann Whitney U test. Receiver operating characteristic curves were used to analyze the sensitivity and specificity of mean corpuscular hemoglobin and platelet distribution width ratio (MPR) and monocyte and hemoglobin ratio (MHR) indicators. The correlation between MPR and MHR and disease severity of KOA was determined by bivariate regression analysis. Independent predictors of disease severity in patients with KOA were assessed by multivariate regression analysis.MPR, MHR, and WOMAC were significantly higher in the KOA group. The ROC curve indicated that the cutoff values of MPR and MHR were 2.09 and 0.0030, respectively, with sensitivity of 86.4% and 68.5% and specificity of 99.2% and 79.4%. Bivariate regression analysis found that MPR was better correlated with disease severity than MHR. The results of multivariate regression analysis demonstrated that the MPR values of moderate and severe patients were more than 19 times that of mild patients, and the OR values were 21.695 and 19.558, respectively.MPR and MHR demonstrated a good correlation with disease severity in patients with KOA. MPR is a potential independent predictor of disease severity in patients with KOA.

Background Integrins play a prominent role in osteogenic differentiation by transmitting both mechanical and chemical signals. Integrin expression is closely associated with tensile stress, which has a positive effect on osteogenic differentiation. We investigated the relationship between integrin αVβ3 and tensile stress. Methods Human fibroblasts were treated with c (RGDyk) and lentivirus transduction to inhibit function of integrin αVβ3. Y-15, cytochalasin D and verteporfin were used to inhibit phosphorylation of FAK, polymerization of microfilament and function of nuclear YAP, respectively. Fibroblasts were exposed to a cyclic tensile stress of 10% at 0.5 Hz, once a day for 2 h each application. Fibroblasts were harvested on day 4 and 7 post-treatment. The expression of ALP, RUNX2, integrin αVβ3, β-actin, talin-1, FAK, vinculin, and nuclear YAP was detected by Western blot or qRT-PCR. The expression and distribution of integrin αVβ3, vinculin, microfilament and nuclear YAP. Results Cyclic tensile stress was found to promote expression of ALP and RUNX2. Inhibition of integrin αVβ3 activation downregulated the rearrangement of microfilament and the expression of ALP, RUNX2 and nuclear YAP. When the polymerization of microfilament was inhibited the expression of ALP, RUNX2 and nuclear YAP were decreased. The phosphorylation of FAK induced by cyclic tensile stress reduced by the inhibition of integrin αVβ3. The expression of ALP and RUNX2 was decreased by inhibition of phosphorylation of FAK and inhibition of nuclear YAP. Conclusions Cyclic tensile stress promotes osteogenesis of human fibroblasts via integrin αVβ3-microfilament axis. Phosphorylation of FAK and nuclear YAP participates in this process.

Background Adipose-derived stem cells (ASCs) are obtained from a variety of sources in vivo where they present in large quantities. These cells are suitable for use in autologous transplantation and the construction of tissue-engineered adipose tissue. Studies have shown that ASCs differentiation is in a high degree of heterogeneity, yet the molecular basis including key regulators of differentiation remains to clarify. Methods We performed single-cell RNA sequencing and bioinformatics analysis on both undifferentiated (ASC-GM group) and adipogenically differentiated human ASCs (ASC-AD group, ASCs were cultured in adipogenic inducing medium for 1 week). And then, we verified the results of serum amyloid A1 (SAA1) with western blotting, immunofluorescence staining, oil red O staining. After these experiments, we down-regulated the expression of serum amyloid A1 (SAA1) gene to verify the adipogenic differentiation ability of ASCs. Results In single-cell RNA sequence analyzing, we obtained 4415 cells in the ASC-GM group and 4634 cells in the ASC-AD group. The integrated sample cells could be divided into 11 subgroups (0–10 cluster). The cells in cluster 0, 2, 5 were came from ASC-GM group and the cells in cluster 1, 3, 7 came from ASC-AD group. The cells of cluster 4 and 6 came from both ASC-GM and ASC-AD groups. Fatty acid binding protein 4, fatty acid binding protein 5, complement factor D, fatty acid desaturase 1, and insulin like growth factor binding protein 5 were high expressed in category 1 and 7. Regulation of inflammatory response is the rank 1 biological processes. And cellular responses to external stimuli, negative regulation of defense response and acute inflammatory response are included in top 20 biological processes. Based on the MCODE results, we found that SAA1, C-C Motif Chemokine Ligand 5 (CCL5), and Annexin A1 (ANXA1) significantly highly expressed during adipogenic differentiation. Western blot and immunofluorescent staining results showed that SAA1 increased during adipogenesis. And the area of ORO positive staining in siSAA1 cells was significantly lower than in the siControl (negative control) cells. Conclusions Our results also indicated that our adipogenic induction was successful, and there was great heterogeneity in the adipogenic differentiation of ASCs. SAA1 with the regulation of inflammatory response were involved in adipogenesis of ASCs based on single-cell RNA sequencing analysis. The data obtained will help to elucidate the intrinsic mechanism of heterogeneity in the differentiation process of stem cells, thus, guiding the regulation of self-renewal and differentiation of adult stem cells.

Epilepsy is a severe neural disorder that affects approximately fifty million individuals globally. Despite the fact that for most of the people with epilepsy, convulsions are better controlled by current accessible antiepileptic medicines, yet there are more than 30% of individuals affected with medically intractable epilepsy and around 30-40% of all patients with epilepsy affected by many adverse reactions and convulsion resistance to the present antiepileptic drugs. Consequently, various scientists attempt to develop new strategies to treat epilepsy, for instance, to find out novel antiepileptic ingredients from traditional medicines. This work aims to present a complete summary of natural medicines prescribed as antiepileptic agents all over the world by ethnic groups and different tribes. We undertook an extensive bibliographic analysis by searching peer reviewed papers and classical textbooks and further consulting well accepted worldwide scientific databases. We carried out PubMed, EMbase and CENTRAL searches by means of terms such as "antiepileptic" and "anti-convulsant" activity of plants. Medicinal plants have been prescribed to treat epilepsy and have been recognized as antiepileptic medicines. In this review, a variety of herbs have been reviewed for thorough studies such as Cuminum cyminum, Butea monosperma, Solanum americanum, Anacyclus pyrethrum, Leonotis leonurus, Elaeocarpus ganitrus and Angelica archangelica. This paper shows that it was high time experimental studies are increased to obtain novel potential active principles from medicinal plants. Plant extracts and their chemical constituents should be further evaluated to clarify their mechanisms of action. This paper provides a solid base upon which to further investigate the clinical efficacy of medicinal plants that are both currently prescribed by physicians as traditional antiepileptic agents, but also could be effective as an antiepileptic drug with further research and study.

Human skin fibroblasts (HSFs) approximate the multidirectional differentiation potential of mesenchymal stem cells, so they are often used in differentiation, cell cultures, and injury repair. They are an important seed source in the field of bone tissue engineering. However, there are a few studies describing the mechanism of osteogenic differentiation of HSFs. Here, osteogenic induction medium was used to induce fibroblasts to differentiate into osteoblasts, and the role of the mechanical sensitive element PDLIM5 in microfilament-mediated osteogenic differentiation of human fibroblasts was evaluated. The depolymerization of microfilaments inhibited the expression of osteogenesis-related proteins and alkaline phosphatase activity of HSFs, while the polymerization of microfilaments enhanced the osteogenic differentiation of HSFs. The evaluation of potential protein molecules affecting changes in microfilaments showed that during the osteogenic differentiation of HSFs, the expression of PDLIM5 increased with increasing induction time, and decreased under the state of microfilament depolymerization. Lentivirus-mediated PDLIM5 knockdown by shRNA weakened the osteogenic differentiation ability of HSFs and inhibited the expression and morphological changes of microfilament protein. The inhibitory effect of knocking down PDLIM5 on HSF osteogenic differentiation was reversed by a microfilament stabilizer. Taken together, these data suggest that PDLIM5 can mediate the osteogenic differentiation of fibroblasts by affecting the formation and polymerization of microfilaments.

Dendritic cells release bioactive exosomes involved in immune regulation. Long non-coding RNAs (lncRNAs) are implicated in a number of immunoregulatory mechanisms. However, the roles of lncRNAs in dendritic cell-derived exosomes remain to be elucidated. The present study aimed to investigate the roles of lncRNAs in exosomes derived from mature and immature dendritic cells and to find specific lncRNAs with immunoregulatory function. The expression profiles of lncRNAs in exosomes derived from bone marrow dendritic cells of C57 mice were illustrated. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Gene Set Enrichment Analysis were performed to identify potential targets correlated with immune regulation. In addition, lncRNA-miRNA-mRNA networks were predicted using bioinformatics methods. Representative lncRNAs were further validated via reverse transcription-quantitative PCR. A total of 437 lncRNAs were analyzed using RNA-seq. Among these, the expression of ~87 lncRNAs was upregulated and 21 lncRNAs was downregulated in mature dendritic cell-derived exosomes (Dex) compared with immature Dex. GO analyses indicated the involvement of upregulated lncRNAs in multiple biological functions, such as the immune system process, while downregulated lncRNAs were involved in poly(A) RNA binding. Analysis of the KEGG pathway identified the relationship of TNF signaling and ribosome pathway with upregulated lncRNAs and downregulated lncRNAs, respectively. The results of gene set enrichment analysis identified that three lncRNA-associated transcripts (Procr-203, Clec4e-202 and Traf1-203) were highly associated with immunoregulatory functions including T helper cell differentiation and Janus kinase-STAT signaling pathway. The results indicated the involvement of candidate lncRNAs in immunoregulation and suggested a new perspective on the modulation of lncRNAs in Dex.

Mesenchymal stem cells (MSCs) have the capacity to differentiate into multiple lineages including osteogenic and adipogenic lineages. An increasing number of studies have indicated that lineage commitment by MSCs is influenced by actin remodeling. Moreover, actin has roles in determining cell shape, nuclear shape, cell spreading, and cell stiffness, which eventually affect cell differentiation. Osteogenic differentiation is promoted in MSCs that exhibit a large spreading area, increased matrix stiffness, higher levels of actin polymerization, and higher density of stress fibers, whereas adipogenic differentiation is prevalent in MSCs with disrupted actin networks. In addition, the mechanical properties of F-actin empower cells to sense and transduce mechanical stimuli, which are also reported to influence differentiation. Various biomaterials, mechanical, and chemical interventions along with pathogen-induced actin alteration in the form of polymerization and depolymerization in MSC differentiation were studied recently. This review will cover the role of actin and its modifications through the use of different methods in inducing osteogenic and adipogenic differentiation.

Coronavirus Disease 2019 (CoViD-19) is the third type of coronavirus disease after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that appears in human population from the past two decades. It is highly contagious and rapidly spread in the human population and compelled global public health institutions on high alert. Due to genetic similarity of this novel coronavirus 2019 with bat virus its emergence from bat to humans is possible. The virus survive in the droplets of coughing and sneezing and spread around the large areas through infected person resulting in its rapid spread among people. Clinical symptoms of CoViD-19 include fever, dry cough, dyspnea, loose stool, nausea and vomiting. The present review discuss the origin of CoViD-19, its rapid spread, mortality rate and recoveries ratio around the world. Since its origin from Wuhan, the CoViD-19 spread very rapidly all across the countries, on April 17, 2020 this disease has affected 210 countries of the globe. The data obtained showed over 2.4 million confirmed cases of CoViD-19. Higher mortality rate was found in Algeria and Belgium as 15% and 13.95%, respectively. Lower mortality rate was found in Qatar 0.17% and Singapore 0.2%. Recovery versus deceased ratio showed that recovery was 68, 59 and 35 times higher than the death in Singapore, Qatar and Thailand respectively. It is concluded that 2019-novel corona virus is a zoonotic pathogen similar to MERS and SARS. Therefore, a barrier should be maintained between and across the human, household and wild animals to avoid such pandemics.

Background:Actin is an essential cellular protein that assembles into microfilaments and regulates numerous processes such as cell migration, maintenance of cell shape, and material transport. In this study, we explored the effect of actin polymerization state on the osteogenic differentiation of human adipose-derived stem cells (hASCs). Methods:The hASCs were treated with different concentrations (0, 1, 5, 10, 20, and 50 nM)of jasplakinolide (JAS), a reagent that directly polymerizes F-actin.The effects ofthe actin polymerization state on cell proliferation, apoptosis, migration, and the maturity of focal adhesion-related proteins were assessed. In addition, western blotting and alizarin red staining assays were performed to assess osteogenic differentiation. Results: These results revealed that cell proliferation and migration in the JAS (0, 1, 5, 10, and 20 nM) groupswashigher than that inthe control group andthe JAS (50 nM) group.The protein expressionof focal adhesion kinase, vinculin, paxillin, and talinwere highest in the JAS (20 nM) group, whilezyxin expression was highestinthe JAS (50 nM) group.Western blottingshowed thatosteogenic differentiation in theJAS (0, 1, 5, 10, 20, and 50 nM) groupswas enhanced compared with that in thecontrol group, and was strongest inthe JAS (50 nM) group.Conclusions: Our data suggest thatthe actinpolymerization state may promote the osteogenic differentiation of hASCs by regulating the protein expression of focal adhesion-associated proteins in a concentration-dependent manner. Our findings provide valuable information for exploring the mechanism of osteogenic differentiationin hASCs.

Background The physical factors of the extracellular matrix have a profound influence on the differentiation behavior of mesenchymal stem cells. In this study, the effect of the biophysical microenvironment on rat bone marrow mesenchymal stem cell (BMSC) osteogenesis was studied both in vitro and in vivo. Methods To prepare cell culture scaffolds of varying stiffness, increasing amounts of hydroxyapatite (HAp) were mixed into a polyethylene glycol/silk fibroin (PEG/SF) solution. The amount of HAp ranged from 25 to 100 mg, which provided for different ratios between HAp and the PEG/SF composite. In vitro, the effect of stiffness on the osteogenic differentiation of rat BMSCs was studied. The outcome measures, which were verified in vivo, included the protein expression of runt-related transcription factor 2 and osteocalcin, alkaline phosphatase activity, and the mRNA expression of osteogenesis-related markers. Results Increasing amounts of HAp resulted in an increased elastic modulus of the cell culture scaffolds. The PEG/SF/HAp fabricated with HAp (50 mg) significantly increased cell adhesion and viability (p p Conclusions We developed a novel cell culture scaffold and demonstrated that substrate stiffness influenced the osteogenic differentiation of rat BMSCs.

Coronavirus Disease 2019 (CoViD-19) is the third type of coronavirus disease after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that appears in human population from the past two decades. It is highly contagious and rapidly spread in the human population and compelled global public health institutions on high alert. Due to genetic similarity of this novel coronavirus 2019 with bat virus its emergence from bat to humans is possible. The virus survive in the droplets of coughing and sneezing and spread around the large areas through infected person resulting in its rapid spread among people. Clinical symptoms of CoViD-19 include fever, dry cough, dyspnea, loose stool, nausea and vomiting. The present review discuss the origin of CoViD-19, its rapid spread, mortality rate and recoveries ratio around the world. Since its origin from Wuhan, the CoViD-19 spread very rapidly all across the countries, on April 17, 2020 this disease has affected 210 countries of the globe. The data obtained showed over 2.4 million confirmed cases of CoViD-19. Higher mortality rate was found in Algeria and Belgium as 15% and 13.95%, respectively. Lower mortality rate was found in Qatar 0.17% and Singapore 0.2%. Recovery versus deceased ratio showed that recovery was 68, 59 and 35 times higher than the death in Singapore, Qatar and Thailand respectively. It is concluded that 2019-novel corona virus is a zoonotic pathogen similar to MERS and SARS. Therefore, a barrier should be maintained between and across the human, household and wild animals to avoid such pandemics. doi: https://doi.org/10.12669/pjms.36.COVID19-S4.2660 How to cite this:Noor AU, Maqbool F, Bhatti ZA, Khan AU. Epidemiology of CoViD-19 Pandemic: Recovery and mortality ratio around the globe. Pak J Med Sci. 2020;36(COVID19-S4):COVID19-S79-S84. doi: https://doi.org/10.12669/pjms.36.COVID19-S4.2660 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Bidirectional molecular movements between the nucleus and cytoplasm take place through nuclear pore complexes (NPCs) embedded in the nuclear membrane. These macromolecular structures are composed of several nucleoporins, which form seven different subcomplexes based on their biochemical affinity. These nucleoporins are integral components of the complex, not only allowing passive transport but also interacting with importin, exportin, and other molecules that are required for transport of protein in various cellular processes. Transport of different proteins is carried out either dependently or independently on transport receptors. As well as facilitating nucleocytoplasmic transport, nucleoporins also play an important role in cell differentiation, possibly by their direct gene interaction. This review will cover the general role of nucleoporins (whether its dependent or independent) and nucleocytoplasmic transport receptors in cell differentiation.

Additional file 17: Table S1. Young’s modulus of the scaffolds with different concentration of hydroxyapatite (HAp).

Parkinson's disease (PD) is the second common progressive neurodegenerative disease, distressing older men and is prevalent Worldwide.This article is aimed to review the epidemiology, etiology, pathogenesis, clinical manifestation, diagnosis and management of PD.A google search was performed to recognise studies that review the characteristics of PD. Search terms included 'Parkinson's disease', 'epidemiology', 'etiology', 'pathogenesis', 'clinical manifestations', 'diagnosis' and 'management of Parkinson disease'.PD is linked to factors such as environmental chemicals, aging, family history and pesticide exposure such as the use of synthetic heroin. PD is characterised clinically by tremors at rest, postural instability, expressionless countenance, lead pipe rigidity and less commonly cognitive impairment. After 60 years of age, PD is commonly prevalent in 1-% of the population, no racial differences are apparent, but the prevalence of PD is more common in men than women. There has also been a better understanding that the disorder may be linked with major non-motor trouble in addition to the additional generally recognised motor complications. There are various management options for the timely management of PD. As the ailment advances, further management strategies are existing; however, the management of non-motor manifestations and late stage motor complications remains mainly testing and will advantage from additional clinical studies.In this article, we have discussed current progress in the understanding of the epidemiology, clinical manifestations, pathogenesis and management strategies of the disease.

Remote Procedure Call (RPC) is a computing as well as communication model for distributed processes to execute client routines on remote servers in the distributed systems. Due to the evolution of geo-distributed mobile cloud computing systems, mobile devices are exposed to frequent disconnection due to limited battery lifetime, processing capacity and network bandwidth while roaming globally. The existing standard RPC and mobile RPC frameworks are not completely suitable for applications in geo-distributed mobile cloud computing. This paper proposes a novel software architecture and associated algorithms for realizing reliable RPC under global mobility of clients. The stateful server chaining and multiple authentication primitives are employed in the proposed design to achieve security as well as location transparency. The software architecture is implemented on heterogeneous testbed and evaluated with promising results. The heterogeneity of mobile cloud platform is considered in the design by employing specific XDR format enhancing portability. A detailed comparative analysis of the proposed design is included in the paper.

Herein, nonlinear optical properties of superhalogen and superalkali doped phosphorene are investigated by utilizing the density functional theory. Large interaction energies revealed that these complexes are satisfactory stable. Doping materials reduce the bandgap and enhance electronic conduction. Density of states analysis provides a better understanding of the electronic transition from HOMO to LUMO of doped compounds. The dipole and transition dipole moment of all doped molecules is changed. These doped molecules have small transition energies (ΔE) which leads to increase in their hyperpolarizabilities. Doping of superalkali enhances the second hyperpolarizability from 51.99 × 104 to 138.25 × 104 au Electron density difference map analysis provides information on the electronic distribution of doped compounds. TD-DFT analysis reveals that these molecules have absorption in the UV region. All these results have proven that doping of phosphorene is an effective approach in designing efficient nonlinear optical materials.

The impacts of exogenous cannabinoids, such as the chemical constituents of Cannabis sativa like cannabidiol (CBD), on brain regions having a modest number of cannabinoid receptors, for example, the ventromedial hypothalamus, are not yet surely knew. A few researches have shown evidence that ventromedial hypothalamus (VMH) neurons play a role in modulating innate fear-induced behavioural reactions in rodents submitted to experimental models of panic attack, for example those based on prey versus wild snake confrontation paradigm. The panic attack-like state was also potentially induced in laboratory animals by N-Methyl-D-aspartate (NMDA), an excitatory amino acid, which stimulates neurons that organize defensive behavioural reactions in the central nervous system. Despite the fact that CB1 receptor-mediated endocannabinoid signaling mechanism underlies the antiaversive effect of exogenous anandamide in medial hypothalamus, there is still a lack of morphological evidence to support the distribution of CB1 receptors in the VMH. Henceforth, this study was designed to explore the specific pattern of distribution of the CB1 receptors in the VMH and, subsequently, the implication of these receptors in the endocannabinoidmodulated defensive behavioural responses followed by fear-induced antinociception evoked by NMDA microinjected in the VMH. A stainless steel guide-cannula was embedded in the rodent\'s brain coordinated towards VMH by means of stareotaxic surgery. Three different doses of cannabidiol (CBD) were microinjected in the VMH. The most effective dose was used after the pretreatment with the CB1 receptor-antagonist AM251, followed by NMDA microinjection in the VMH. The outcomes demonstrated that the defensive behavioural responses evoked in response to intra-VMH administration of NMDA (6 nmol) were decreased by intra-hypothalamic microinjections of CBD at the highest dose (100 nmol).These effects, however, were blocked by the administration of the CB1 receptor-antagonist AM251 (100 pmol) in the VMH. In addition, the fear-induced antinociception elicited by VMH chemical stimulation diminished after the VMH treatment with CBD, an effect reversed by the intra-diencephalic pretreatment with AM251. These findings suggested that CBD causes panicolytic-like effects when administered in the VMH, and that antiaversive effect recruits the CB1 receptor-endocannabinoid signaling mechanism in VMH. O papel dos canabinoides exógenos nas regiões do cérebro com um número modesto de receptores cannabinoides, por exemplo, o hipotálamo ventromedial, ainda não está plenamente esclarecido. Algumas pesquisas de nosso grupo, não obstante, mostraram o hipotálamo ventromedial (HVM) exerce modulação de reações comportamentais provocadas pelo medo inato em animais submetidos a um modelo de ataques de pânico. Crises de pânico foram induzidas em animais de laboratório por N-metil-D-aspartato (NMDA), um aminoácido excitatório que, ao ser microinjetado em estruturas do sistema encefálico de aversão, estimula reações comportamentais defensivas no sistema nervoso central que mimetizam as respostas defensivas eliciadas por roedores confrontados com serpentes. Apesar do mecanismo de sinalização endocanabinoide mediado pelos receptores CB1 desempenhar um papel na modulação da neurotransmissão excitadora e inibitória no SNC, ainda há escassez de evidências morfológicas que embasem a distribuição dos receptores CB1 no HVM. Por conseguinte, este estudo foi idealizado para explorar a forma específica de distribuição dos receptores CB1 no HVM e, posteriormente, estudar a implicação desses receptores na modulação de respostas comportamentais defensivas, seguidas por antinocicepção induzida pelo medo, moduladas por endocanabinoides e evocadas por microinjetação de NMDA no HVM. Uma cânula-guia feita de aço inoxidável foi implantada no cérebro do roedor, e direcionada para o HVM por meio de cirurgia estareotóxica. Três diferentes doses de cannabidiol (CBD) foram microinjetadas no HVM. A dosagem mais eficaz foi utilizada após o pré-tratamento do hipotálamo medial com um antagonista do receptor CB1, o AM251, seguido da microinjeção NMDA no HVM. Os resultados demonstraram que as respostascomportamentais defensivas evocadas em resposta à administração intra-HVM de NMDA (6 nmol) foram diminuídas por microinjeções intra-hipotalâmicas de CBD na dose mais alta (100 nmol). Estes efeitos, no entanto, foram atenuados pela administração do antagonista do receptor CB1, AM251, na dose de 100 pmol no HVM. Além disso, a antinocicepção induzida pelo medo foi atenuada pela administração intra-diencefálica de CBA, o que foi revertido pelo pré-tratamenot do HVM com AM251. Esses dados sugerem que o CBD causa efeitos panicolíticos, quando administrado no HVM, envolvendo o mecanismo de sinalização do receptor CB1-endocannabinoide.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Avian haemosporidian is a diverse group of protozoan parasites including Plasmodium and Haemoproteus that can infect birds and use a variety of Diptera vectors for their transmission. It has been known that host traits and annual seasonal cycles may influence infection rates of these parasites in bird communities. However, in the Neotropics such influence remains to be determined. We examined the effect of temporal dynamic and host traits on the prevalence and diversity of avian haemosporidian parasites in the Brazilian avifauna of the Caatinga biome. A total of 933 samples were molecularly screened for the presence of Plasmodium/Haemoproteus infections. We found high avian haemosporidian prevalence (51.3%; n=481/933) varying according to temporal dynamic with the highest prevalence (61%) observed in the beginning of dry season. Prevalence also varied among the 20 well-sampled host species within a range from 0 to 70%. The host functional traits (feeding behavior, flocking behavior, habitat use and nest type) were associated with infection rate for Haemoproteus (Haemoproteus), with high infection rates observed for granivorous, single species flock, forest habitat independent, and open cup nester birds. For Haemoproteus (Parahaemoproteus) and Plasmodium infection, none correlation with host functional traits was observed. After excluding the large sample size of Columbiformes (n=462/933), Plasmodium infection rate showed association with feeding behavior, nest type and migratory behavior. Subsequent to parasite screening and prevalence determination, sequencing PCR was performed to determine parasite lineage diversity. Parasite community was composed of 32 distinct lineages, including 7 new lineages, pointing to high haemosporidian diversity in the Caatinga biome when compared to other studies in seasonally dry ecosystems. Interestingly, our results suggest that avian host traits are important determinants of prevalence and diversity of avian haemosporidian parasite in Caatinga biome. We also analyzed the diversity and distribution of avian haemosporidian lineages on a broad scale across a diverse range of avian hosts in seven ecologically distinct habitats in Brazil. Plasmodium was the most common parasite group in Brazil, accounting for 67% of the recovered lineages and that pattern was observed in five out of the seven habitats evaluated here. However, H. (Haemoproteus) was the most common parasite among birds from the Caatinga biome while H. (Parahaemoproteus) was prevalent in Restinga habitat, Among the 69 well-sampled lineages (lineages detected at minimum of four times), 48 were habitat-generalist (36 Plasmodium, seven H. (Parahaemoproteus), and five H. (Haemoproteus), occurring in two or more host species or habitats. Plasmodium lineages showed a broader host and habitat range when compared to H. (Parahaemoproteus) and H. (Haemoproteus). Interestingly, we found 14 Plasmodium lineages that were host and habitat specialist. Our results suggest the existence of both host and habitat generalist and specialist lineages in the two main genera, Plasmodium and Haemoproteus, in Brazil. Further studies are required aiming to understand the factors influencing the way avian haemosporidian parasites colonize bird communities in the Neotropical region. Hemosporídios aviários são um grupo diverso de parasitos protozoários, que incluem os gêneros Plasmodium e Haemoproteus. Estes parasitos podem infectar aves e usar uma variedade de dípteros como vetores para sua transmissão. Sabe-se que características do hospedeiro e ciclos sazonais anuais podem influenciar a taxa de infecção desses organismos. Entretanto, tais efeitos em hemosporídeos de aves neotropicais ainda precisam ser determinados. Examinamos o efeito da dinâmica temporal e características do hospedeiro na prevalência e diversidade de hemosporídeos aviários na avifauna brasileira do bioma Caatinga. Um total de 933 amostras foram testadas quanto à presença de infecções por Plasmodium / Haemoproteus. Encontramos alta prevalência de hemosporídeos nas aves (51.25%; n = 481/933) variando de acordo com a dinâmica temporal. A maior prevalência (61%) foi observada no início da estação seca. A prevalência também variou entre as 20 espécies hospedeiras bem amostradas variando de 0 a 70%. A história de vida do hospedeiro (comportamento alimentar, comportamento de flocagem, uso de habitat e tipo de ninho) também foram associadas à taxa de infecção por Haemoproteus (Haemoproteus). Altas taxas de infecção foram observadas para aves granívoras, bandos compostos por uma única espécie, com habitats independentes de florestas e com ninhos do tipo aberto. Para a infecção por Haemoproteus (Parahaemoproteus) e Plasmodium, não foi observada nenhuma correlação com as características da história de vida do hospedeiro. Após excluir amostras de Columbiformes (n = 462/933), a taxa de infecção por Plasmodium mostrou associação com comportamento alimentar, tipo de ninho e comportamento migratório. Após o diagnostico fizemos uma PCR de sequenciamento para verificar a diversidade de linhagens de parasitos. A comunidade de parasitos foi composta por 32 linhagens distintas, sendo que dessas 7 são novas. Este resultado demonstra uma alta diversidade de hemosporídeos na Caatinga quando comparada a outras fitofisionomias brasileiras em ecossistemas sazonalmente secos. Também analisamos a diversidade e distribuição de linhagens haemosporidianas de aves em larga escala de ampla gama de hospedeiros aviários em sete habitats ecologicamente distintos no Brasil. Plasmodium foi o grupo parasitário mais comum no Brasil, representando 67% das linhagens recuperadas e esse padrão foi observado em cinco dos sete habitats aqui avaliados. Entretanto, o H. (Haemoproteus) foi o parasito mais comum entre as aves do bioma Caatinga, enquanto o H. (Parahaemoproteus) foi prevalente no habitat de Restinga. Entre as 69 linhagens amostradas (linhagens detectadas no mínimo quatro vezes), 48 eram de habitat geralista (36 Plasmodium, sete H. (Parahaemoproteus), e cinco H. (Haemoproteus), ocorrendo em duas ou mais espécies hospedeiras ou habitats. As linhagens de Plasmodium mostraram mais ampla gama de hospedeiro e habitats quando comparadas com H. (Parahaemoproteus) e H. (Haemoproteus). Encontramos 14 linhagens de Plasmodium que foram hospedeiras especialistas em habitats especializados. Os resultados sugerem a existência de linhagens hospedeiras generalistas de habitat especializados nos dois principais gêneros, Plasmodium e Haemoproteus, no Brasil. Mais estudos são necessários para entender os fatores que influenciam a forma como os parasitos haemosporidianos colonizam as comunidades de aves na região Neotropical.