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INTRODUCTION: The molecular transformation of the human preaccess vein after arteriovenous fistula (AVF) creation is poorly understood. This limits our ability to design efficacious therapies to improve maturation outcomes. METHODS: Bulk RNA sequencing (RNA-seq) followed by paired bioinformatic analyses and validation assays were performed in 76 longitudinal vascular biopsies (veins and AVFs) from 38 patients with stage 5 chronic kidney disease or end-stage kidney disease undergoing surgeries for 2-stage AVF creation (19 matured, 19 failed). RESULTS: A total of 3637 transcripts were differentially expressed between veins and AVFs independent of maturation outcomes, with 80% upregulated in fistulas. The postoperative transcriptome demonstrated transcriptional activation of basement membrane and interstitial extracellular matrix (ECM) components, including preexisting and novel collagens, proteoglycans, hemostasis factors, and angiogenesis regulators. A postoperative intramural cytokine storm involved >80 chemokines, interleukins, and growth factors. Postoperative changes in ECM expression were differentially distributed in the AVF wall, with proteoglycans and fibrillar collagens predominantly found in the intima and media, respectively. Interestingly, upregulated matrisome genes were enough to make a crude separation of AVFs that failed from those with successful maturation. We identified 102 differentially expressed genes (DEGs) in association with AVF maturation failure, including upregulation of network collagen VIII in medial smooth muscle cells (SMCs) and downregulation of endothelial-predominant transcripts and ECM regulators. CONCLUSION: This work delineates the molecular changes that characterize venous remodeling after AVF creation and those relevant to maturation failure. We provide an essential framework to streamline translational models and our search for antistenotic therapies.

Due to drug addiction and the emergence of antibiotic resistance in pathogens, the disease load and medication intake have risen worldwide. The alternative treatment for drug-resistant infections is Nano formulation-based antimicrobial agents. The plant extract of Conocarpus Lancifolius fruits was used to synthesize silver nanoparticles in the current study, and it was further employed as an antimicrobial and anticancer agent. Nanoparticles have been characterized by UV–visible spectrometer revealed the notable peak of λmax = 410–442 nm, which confirms the reduction of silver ion to elemental silver nanoparticles, and the biological moieties in the synthesis were further confirmed by FTIR analysis. The stability and crystalline nature of materials were approved by XRD analysis and expected the size of the nanomaterials of 21 to 173 nm analyzed by a nanophox particle-size analyzer. In vitro, synthesized materials act as an antibacterial agent against Streptococcus pneumonia and Staphylococcus aureus. The inhibition zones of 18 and 24 mm have been estimated to be antibacterial activity against both bacteria. The potency of up to 100% of AgNPs for bacterial strains was incubated overnight at 60 μg/ml. Based on our results, biogenic AgNPs reveal significant activity against fungal pathogen Rhizopusus stolonifera and Aspergillus flavus that cause leading infectious diseases. Additionally, nanomaterials were biocompatible and demonstrated the potential anticancer activities against MDA MB-231 cells after 24-hour exposure.

Herein, we reported a facile, cost efficient, synthesis of Gr@NiCu NCs nanocomposite and explored their application in supercapacitor and antibacterial applications. The Graphene sheets in the NiCu based electrode showed a high specific surface area and supports conductive networks decorated with oxygen groups, which synergistically improve charge storage capability. Furthermore, Gr@NiCu NCs contain hydrophilic oxygen groups of chemically reduced graphene oxide, which allows easy access of the electrolyte to the electrode’s pores. An electrochemical study demonstrated the highest specific capacitance of 977 Fg−1 at 10 Ag-1 and remarkable cyclic retentiveness ∼90% even after 1000 cycles. A noteworthy energy density of the Gr@NiCu NCs achieves approximately 542 KWh kg−1 and a power density of 21 kW kg−1 acquired through the CD description utilizing a current density of 10 Ag-1. The antimicrobial activity of synthesized Gr@NiCu NCs was performed against S. Aureus, E. coli, and MRSA ATCC BAA 1708, P.Aeroginosa (ATCC 27853), S.Mutans (MTCC SM 497) strains compared with ampicillin antibiotic drug. This potent antibacterial activity is attributable to the synergistic apoptosis from Cu2+ and bacteriostatic effect Ni2+ ions with graphene sheet (enhance ROS production), released from Gr@NiCu NCs.

Background Glioblastoma multiforme (GBM) is one of the most daunting issues to modern therapeutics, with a higher mortality rate post-diagnosis. Temozolomide (TMZ) is the only available treatment; however, the frequent resistance leaves the oncologists at a dead end. Therefore, new approaches to circumvent the GBM are highly desired. We have employed TiO2 nanosticks loaded with TMZ as nanomedicine for TMZ-resistant GBM resection in this contribution. Results The ultrasonication triple-action effect could greatly facilitate tumor ablation by enhancing the TiO2 nanosticks traversing across BBB, releasing the TMZ payload from TiO2 nanosticks and reactive oxygen species (ROS) generation from TiO2 nanosticks within the GBM milieu. The tumor ablation was confirmed by MTT and Annexin(v)-PI assays, apoptotic proteins expression via western blot and ROS level detection in vitro, whereas tumor volume, weight, survival rate, and relative photon flux in the xenograft and orthoptic TMZ-resistant GBM murine models as in vivo. Conclusion We found this nanomedicine-based ultrasound modality highly efficient in GBM treatment and is of future clinical application value due to the employment of already FDA-approved techniques and nanomedicine.

Autophagy plays an intricate role in paradigmatic human pathologies such as cancer, and neurodegenerative, cardiovascular, and autoimmune disorders. Autophagy regulation is performed by a set of autophagy-related (ATG) genes, first recognized in yeast genome and subsequently identified in other species, including humans. Several other genes have been identified to be involved in the process of autophagy either directly or indirectly. Studying the codon usage bias (CUB) of genes is crucial for understanding their genome biology and molecular evolution. Here, we examined the usage pattern of nucleotide and synonymous codons and the influence of evolutionary forces in genes involved in human autophagy. The coding sequences (CDS) of the protein coding human autophagy genes were retrieved from the NCBI nucleotide database and analyzed using various web tools and software to understand their nucleotide composition and codon usage pattern. The effective number of codons (ENC) in all genes involved in human autophagy ranges between 33.26 and 54.6 with a mean value of 45.05, indicating an overall low CUB. The nucleotide composition analysis of the autophagy genes revealed that the genes were marginally rich in GC content that significantly influenced the codon usage pattern. The relative synonymous codon usage (RSCU) revealed 3 over-represented and 10 under-represented codons. Both natural selection and mutational pressure were the key forces influencing the codon usage pattern of the genes involved in human autophagy.

During a cytokine storm, dysregulated proinflammatory cytokines are produced in excess. Cytokine storms occur in multiple infectious diseases, including Coronavirus 2019 (COVID-19). Thus, eliminating cytokine storms to enhance patient outcomes is crucial. Given the numerous cytokines involved, individual therapies might have little effect. Traditional cytokines might be less effective than medicines that target malfunctioning macrophages. Nanomedicine-based therapeutics reduce cytokine production in animal models of proinflammatory illnesses. The unique physicochemical features and controlled nano-bio interactions of nanotechnology show promise in healthcare and could be used to treat several stages of this virus-induced sickness, including cytokine storm mortality. Macrophage-oriented nanomedicines can minimize cytokine storms and associated harmful effects, enhancing patient outcomes. Here, we also discuss engineering possibilities for enhancing macrophage efficacy with nanodrug carriers.

Alzheimer's disease (AD) is a complex neurodegenerative disease leading to progressive loss of memory that mainly affects people above 60 years of age. It is one of the leading causes of deaths in the USA. Given its inherent heterogeneity and a still-incomplete understanding of its pathology, biomarkers, and targets available for therapy, it is a challenge to design an effective therapeutic strategy. Several hypotheses have been proposed to understand the disease and to identify reliable markers and targets for treatments. However, none have resulted in strong support from clinical trials. In this review, we objectively discuss the various therapeutic strategies and mechanistic approaches to improve the current clinical outcome of AD therapy.

In this manuscript, Fe3O4 nanoparticles (NPs) were prepared by using a simple cost-effective domestic microware based chemical route. The Crystal structure of Fe3O4 nanoparticles studied using X-ray diffraction and selective area electron diffraction pattern clearly showed that Fe3O4 NPs exhibited single-phase FCC structures. The average crystallite size calculated using the XRD pattern and TEM micrographs was found to be ∼7 and ∼12 nm, respectively. The magnetic hysteresis loop measured at room temperature inferred that Fe3O4 NPs exhibited the soft ferromagnetic behavior. The nanoparticles then immobilized with Pseudomonas aeruginosa strain JS11. Bacteria have contemporaneous plant growth and biocontrol potential viz indole acetic acid (IAA) production, tri-calcium phosphate solubilization in Pikovskaya’s medium. These auxiliary activities of strain showed remarkable capability in the presence of Fe3O4 NPs at different concentrations. The IAA assay revealed the presence of Fe3O4 NPs (50 and 100 ng mL-1) increased the production of about 26.1 and 27.9 μg mL-1 of IAA, respectively, as compared to 22 μg mL-1 IAA in the medium. Phosphate solubilization also increased in the presence of Fe3O4 NPs 100 ng‘mL-1 as compared to the control. Production of siderophores and antibiotic phenazine-1-carboxylic acid (PCA) production in bacterial cell culture was determined. Thus, the increase in auxiliary biological activities viz. IAA production, phosphate solubilization, siderophores, and PCA production in the presence of Fe3O4 NP stratifies the better plant growth and biocontrol activities in agricultural soils.

Nanotechnology is the study of developing peculiar particles (1-100 nanometres (nm)) of matter at an atomic, molecular, and supramolecular scale.

Protein aggregation and amyloidogenesis have been associated with several neurodegenerative disorders like Alzheimer’s, Parkinson’s etc. Unfortunately, there are still no proper drugs and no effective treatment available. Due to the unique properties of noble metallic nanoparticles, they have been used in diverse fields of biomedicine like drug designing, drug delivery, tumour targeting, bio-sensing, tissue engineering etc. Small-sized silver nanoparticles have been reported to have anti-biotic, anti-cancer and anti-viral activities apart from their cytotoxic effects. The current study was carried out in a carefully designed in-vitro to observe the anti-amyloidogenic and inhibitory effects of biologically synthesized green silver nanoparticles (B-AgNPs) on human serum albumin (HSA) aggregation taken as a model protein. We have used different biophysical assays like thioflavin T (ThT), 8-Anilino-1-naphthalene-sulphonic acid (ANS), Far-UV CD etc. to analyze protein aggregation and aggregation inhibition in vitro. It has been observed that the synthesized fluorescent B-AgNPs showed inhibitory effects on protein aggregation in a concentration-dependent manner reaching a plateau, after which the effect of aggregation inhibition was significantly declined. We also observed meaningful chaperone-like aggregation-inhibition activities of as-synthesized florescent B-AgNPs in astrocytes.

Background: Coronavirus disease 2019 (COVID-19) is a global health threat and caused a universal psychosocial impact on the general population. Therefore, the knowledge, attitude, and perceptions (KAPs) of the general population are critical for the development and effective implementation of standard operating procedures (SOP) to contain the contagion and minimize the losses. Therefore, the current study was conducted to understand and evaluate the KAPs of Pakistani populations toward the COVID-19.Methods: An online cross-sectional study was carried out among participants from 1 May to 30 July 2020 in different areas of Pakistan. The respondents of the study were the general population with age ≥ 18 years. The poll URL was posted on several channels after a call for participation. Other social media platforms such as WeChat, WhatsApp, Facebook, Twitter, Instagram, Messenger, and LinkedIn were engaged to maximize general population engagement. The questionnaire included details about sociodemographic, knowledge about COVID-19, perceptions toward universal safety precautions of COVID-19, and beliefs attitude toward the COVID-19. The obtained data were exported into a Microsoft Excel spreadsheet and SPSS software version 21 for windows. The descriptive statistics values were presented in frequencies and percentages. Binary logistic regression, Chi-square test, and one-way ANOVA were applied to analyze the participants' socio-demographic characteristics and variables related to KAPs. P-value < 0.05 was recorded as significant.Results: A total of 1,000 participants were invited of which 734 participated in this study. The response rate was 73.4% (734/1,000). The gender, marital status, education, and residence showed a significant association with the knowledge score. The majority of the study participants were thinking that COVID-19 may be more dangerous in elderly individuals 94.5% (n = 700), and individuals with chronic diseases or severe complications 96.7% (n = 710) (p = 0.00). More than half of the participants 52.5% (n = 385) showed their concern that either they or their family members might get the infection. More than 98% (n = 703), (P-value = 0.00) of the participants held that COVID-19 would be successfully controlled in Pakistan by following the standard SOPs and government guidelines.Conclusion: This study showed that the general population of Pakistan has good awareness and reasonable attitudes and perceptions toward the full features of the COVID-19. The current study suggests that mass-level effective health education programs are necessary for developing countries to improve and limit the gap between KAP toward COVID-19.

Mohammad Azam Ansari,1 Sultan Akhtar,2 Mohd Ahmar Rauf,3 Mohammad N Alomary,4 Sami AlYahya,4 Saad Alghamdi,5 MA Almessiere,2,6 Abdulhadi Baykal,7 Firdos Khan,8 Syed Farooq Adil,9 Mujeeb Khan,9 Mohammad Rafe Hatshan9 1Department of Epidemic Disease Research, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 2Department of Biophysics, Institute for Research & Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 3Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA; 4National Centre for Biotechnology, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 5Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; 6Department of Physics, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 7Department of Nanomedicine Research, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 8Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 9Department of Chemistry, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi ArabiaCorrespondence: Mohammad Azam Ansari; Syed Farooq Adil Email maansari@iau.edu.sa; sfadil@ksu.edu.saBackground: The constant rise of microbial biofilm formation and drug resistance to existing antimicrobial drugs poses a significant threat to community health around the world because it reduces the efficacy and efficiency of treatments, increasing morbidity, mortality, and health-care expenditures. As a result, there is an urgent need to develop novel antimicrobial agents that inhibit microbial biofilm formation.Methods: The [Ni0.4Cu0.2Zn0.4](Fe2-xDyx)O4(x≤ 0.04) (Ni-Cu-Zn) nano spinel ferrites (NSFs) have been synthesized by the sol–gel auto-combustion process and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray (EDX) and transmission electron microscopy (TEM). The antimicrobial, antibiofilm and antiproliferative activities of Ni-Cu-Zn NSFs were also examined.Results: The XRD pattern confirms the secondary phase DyFeO3 and Fe2O3 for substituted Dy3+ samples, and the crystallite size ranged from 10 to 19 nm. TEM analysis of NSFs revealed that the particles were cube-shaped and 15nm in size. NSFs exhibited significant antimicrobial, antibiofilm and antiproliferative activity. At concentration of 1 mg/mL, it was found that the NSFs (ie, x=0.0, x=0.01, x=0.02, x=0.03 and x=0.04) inhibit biofilm formation by 27.6, 26.2, 58.5, 33.3 and 25% for methicillin-resistant Staphylococcus aureus (MRSA) and 47.5, 43.5, 48.6, 58.3 and 26.6% for Candida albicans, respectively. SEM images demonstrate that treating MRSA and C. albicans biofilms with NSFs significantly reduces cell adhesion, colonization and destruction of biofilm architecture and extracellular polymeric substances matrices. Additionally, SEM and TEM examination revealed that NSFs extensively damaged the cell walls and membranes of MRSA and C. albicans. Huge ultrastructural alteration such as deformation, disintegration and separation of cell wall and membrane from the cells was observed, indicating significant loss of membrane integrity, which eventually led to cell death. Furthermore, it was observed that NSF inhibited the cancer cell growth and proliferation of HCT-116 in a dose-dependent manner.Conclusion: The current study demonstrated that the synthesized Ni-Cu-Zn NSFs could be used to develop potential antimicrobial surface coatings agents for a varieties of biomedical-related materials and devices in order to prevent the biofilms formation and their colonization. Furthermore, the enhanced antiproliferative properties of manufactured SNFs suggest a wide range of biomedical applications.Keywords: biomedical application, nano spinel ferrites, MRSA, Candida albicans, biofilm, ultrastructural alteration

The ongoing outbreak of coronavirus disease COVID-19 is significantly implicated by global heterogeneity in the genome organization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The causative agents of global heterogeneity in the whole genome of SARS-CoV-2 are not well characterized due to the lack of comparative study of a large enough sample size from around the globe to reduce the standard deviation to the acceptable margin of error. To better understand the SARS-CoV-2 genome architecture, we have performed a comprehensive analysis of codon usage bias of sixty (60) strains to get a snapshot of its global heterogeneity. Our study shows a relatively low codon usage bias in the SARS-CoV-2 viral genome globally, with nearly all the over-preferred codons’ A.U. ended. We concluded that the SARS-CoV-2 genome is primarily shaped by mutation pressure, however, marginal selection pressure cannot be overlooked. Within the A/U rich virus genomes of SARS-CoV-2, the standard deviation in G.C. (42.91% ± 5.84%) and the GC3 value (30.14% ± 6.93%) points towards global heterogeneity of the virus. Several SARS-CoV-2 viral strains were originated from different viral lineages at the exact geographic location also supports this fact. Taking all together, these findings suggest that the general root ancestry of the global genomes are different with different genome’s level adaptation to host. This research may provide new insights into the codon patterns, host adaptation, and global heterogeneity of SARS-CoV-2.

Immunotherapy has gathered momentum in the advanced generation of cancer therapeutics. Many unresectable resistant tumor subtypes are ideal candidates for immunotherapy; however, the efficacy is limited because of heterogeneity of both malignant cells and non-malignant cells of the tumor microenvironment, including stromal and immune cells. The success of immunotherapy is largely dependent on the population of individual immune cell types between patients of the same tumor subtype, and the expression of biomarkers that are expressed by the components of the immune system. Hence, it is imperative to first identify the components of the immune system, visualize these populations in the tumor microenvironment, and then devise specifically targeted immunotherapies. In this review, we have outlined strategies to characterize the cellular components of the immune system with clinically relevant imaging modalities. The importance of high dimensional analyses including mass cytometry and unbiased single-cell RNA sequence analysis in visualizing the ideal candidates for immunotherapy has been discussed. This review stresses the importance of immuno-imaging as a means to further develop targeted immunotherapies for cancer.

Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.

Consumption of silver nanoparticles (AgNPs) has been increased many folds due to its antimicrobial actions resulting in its widespread incorporation into a wide range of biomedical and consumer products. Still, enough research is needed to clearly understand the effect of these nanoparticles on the conformations of important macromolecules like proteins under different pathophysiological conditions. Pointing towards the situation, we carefully designed an in vitro study to elucidate the effect of green AgNPs on the aggregation pattern of α-chymotrypsinogen A at a human pathological body temperature. We observed that the B-AgNPs inhibited the aggregation in αCgn-A in a concentration-dependent manner showing maximum inhibition at 30 μg/ml above which the effect of aggregation inhibition was reduced as evident at 40 and 50 μg/ml concentrations of B-AgNPs. Further, in our in vitro analysis, we found that the B-AgNPs of lower sizes has potential chaperone-like activity at pathological body temperature, which can be used as a component of the drug to prevent protein aggregation after further verification in animal models.

The coronaviruses have caused severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS), and the more recent coronavirus pneumonia (COVID‐19). The global COVID‐19 pandemic requires urgent action to develop anti‐virals, new therapeutics, and vaccines. In this review, we discuss potential therapeutics including human recombinant ACE2 soluble, inflammatory cytokine inhibitors, and direct anti‐viral agents such as remdesivir and favipiravir, to limit their fatality. We also discuss the structure of the SARS‐CoV‐2, which is crucial to the timely development of therapeutics, and previous attempts to generate vaccines against SARS‐CoV and MERS‐CoV. Finally, we provide an overview of the role of nanotechnology in the development of therapeutics as well as in the diagnosis of the infection. This information is key for computational modeling and nanomedicine‐based new therapeutics by counteracting the variable proteins in the virus. Further, we also try to effectively share the latest information about many different aspects of COVID‐19 vaccine developments and possible management to further scientific endeavors., The role of nanotechnology in the detection and the therapeutics of the COVID‐19. The image was created with biorender.com.

Aerogels are special class of porous gel materials in which the liquid part is replaced by gas without shriking the shape of it. Most of the aerogel are based on polysaccharide origins, for example, cellulose, chitosan, alginate, starch, agar aerogels. In terms of biomedical applications, aerogels can also be used for loading and diffusion of antimicrobial drugs and to further control the release of drugs. Silica and cellulose have been widely used in the biomedical field. The aerogels and its composite display controlled drug release behavior and efficient antibacterial performance, thus confirming their potential for biomedical applications. This chapter focuses on bio-aerogels from the viewpoints of loading of antimicrobial agent cellular uptake, toxicity, biodegradability, and the biomedical application perspectives.

In recent studies, polysaccharide-based advanced composite materials applied in biological science have been in high demand because they are biocompatible, inexpensive, and naturally available. These are a long chain of polysaccharide, containing many monosaccharides that are linked to the glycosidic bonds, and are a promising alternative to nonbiodegradable chemical polymers due to biodegradability and sustainability in the ecosystem. Natural polysaccharide has been used to prepare nanocomposite material with metal oxide and carbon-based nanomaterials. The surface area/volume ratio is crucial to understand nanocomposite’s structural property based on polysaccharide. Different types of monosaccharides and polysaccharides from various biological sources, at a nonmetric scale, have been used for the synthesis of nanocomposite materials with low density, high molecular weight, high surface reactivity, and ease of surface modification. There are signs of progress with these materials in preclinical applications for tissue engineering and gene delivery to treat many diseases in both therapeutic and monitoring aspects. These nanocomposite materials can potentially be used in tissue engineering, drug delivery, cellular culture, and any medicine’s slow release. This chapter focuses on the application of nanocomposite materials in tissue engineering and gene delivery.

Nanotechnology is the most promising of the technologies used in research. The production of environmentally friendly biomaterials is an important approach towards the use of these materials in environmental applications. Nowadays, many inorganic nanoparticles with specific chemical composition, size, and morphology can be synthesized using microorganisms, and their use in technical cutting-edge areas has been investigated. This chapter also addresses the synthesis of different forms of inorganic nanoparticles including metallic, oxide, sulfide, and other common nanoparticles. Different modeling strategies for the creation of these nanoparticles will be explained. The methods of regulating particle size and shape are discussed. The applications of these nanostructured molecules in treatment, diagnosis, gene therapy, DNA analysis, antibacterial agents, and biosensors are discussed. The recent discovery of different microbial synthesis methods for inorganic nanoparticles is discussed. We highlight the importance of controlling the critical parameters of biogenic synthesis to allow the biogenic synthesis of nanoparticles.

The COVID-19 pandemic is responsible for an unprecedented disruption to the healthcare systems and economies of countries around the world. Developing novel therapeutics and a vaccine against SARS-CoV-2 requires an understanding of the similarities and differences between the various human coronaviruses with regards to their phylogenic relationships, transmission, and management. Phylogenetic analysis indicates that humans were first infected with SARS-CoV-2 in late 2019 and the virus rapidly spread from the outbreak epicenter in Wuhan, China to various parts of the world. Multiple variants of SARS-CoV-2 have now been identified in particular regions. It is apparent that MERS, SARS-CoV, and SARS-CoV-2 present with several common symptoms including fever, cough, and dyspnea in mild cases, but can also progress to pneumonia and acute respiratory distress syndrome. Understanding the molecular steps leading to SARS-CoV-2 entry into cells and the viral replication cycle can illuminate crucial targets for testing several potential therapeutics. Genomic and structural details of SARS-CoV-2 and previous attempts to generate vaccines against SARS-CoV and MERS have provided vaccine targets to manage future outbreaks more effectively. The coordinated global response against this emerging infectious disease is unique and has helped address the need for urgent therapeutics and vaccines in a remarkably short time.

Fungal Infection is a hidden enemy for mammals because it is inhibiting commonly in nasal and oral mucosa, where it colonizes and starts unwanted growth and form infection. The differentiation between pathogenicity with colonization and regular colonization in upper respiratory system infection is difficult initially. Sometimes fungal infection rate becomes high due to the immune system weakening by the immunosuppressive drugs and old age because of a weak immune system unable to fight opportunistic fungi. The most common fungal infection is an endemic mycosis caused by dimorphic fungal species that are ubiquitously present in the soil and environment of particular geographic regions. Few most common fungal infections are listed Athlete’s foot is caused by a number of different fungi, including species of Trichophyton, Epidermophyton, and Microsporum, Tinea Versicolor, Onychomycosis, Tinea Capitis and Ringworm caused by Dermatophytes, Candidiasis by Candida sp.. In general, fungal skin infection is a more frequent and more recurrent pathogen that often goes hidden by the physician and persistent body. Fungal Infection becomes more serious when it occurred as a secondary infection after bacterial Infection. Frequently simple measures can prevent the hidden fungal Infection and therefore reduce the possibility of complications. This chapter presents information on mysterious diseases caused by different fungi besides some possible ways of protection and treatments.

Background Glioblastoma Multiforme (GBM) is one the most daunting issue to modern therapeutics, with a higher mortality rate post-diagnosis. Temozolomide (TMZ) is the only available treatment; however, the frequent resistance leaves the oncologists at the dead end. Therefore, new approaches to circumvent the GBM are highly desired. In this contribution, we have employed TiO2 nanosticks loaded with TMZ as nanomedicine for TMZ resistant GBM resection. Results The ultrasonication triple action effect could highly facilitate the tumor ablation by enhancing the TiO2 nanosticks traversing across BBB, releasing the TMZ payload from TiO2 nanosticks and Reactive Oxygen Species (ROS) generation from TiO2 nanosticks within GBM milieu. The tumor ablation was confirmed by MTT and Annexin(v)-PI assays, apoptotic proteins expression via western blot and ROS level detection in vitro, whereas tumor volume, weight, survival rate, and relative photon flux in the xenograft and orthoptic TMZ resistant GBM murine models as in vivo. Conclusion We found this nanomedicine-based ultrasound modality highly efficient in GBM treatment and is of future clinical application value due to employment of already FDA approved techniques and nanomedicine.

Sometimes, life-threatening infections are initiated by the biofilm formation facilitated at the infection site by the drug-resistant bacteria

Triple-Negative Breast Cancer (TNBC) is considered as the most onerous cancer subtype, lacking the estrogen, progesterone, and HER2 receptors. Evaluating new markers is an unmet need for improving targeted therapy against TNBC. TNBC depends on several factors, including hypoxia development, which contributes to therapy resistance, immune evasion, and tumor stroma formation. In this study, we studied the curcumin analogue (3,4-Difluorobenzylidene Curcumin, CDF) encapsulated bovine serum albumin (BSA) nanoparticle for tumor targeting. For tumor targeting, we conjugated Acetazolamide (ATZ) with CDF and encapsulated it in the BSA to form a nanoparticle (namely BSA-CDF-ATZ). The in vitro cytotoxicity study suggested that BSA-CDF-ATZ is more efficient when compared to free CDF. The BSA-CDF-ATZ nanoparticles showed significantly higher cell killing in hypoxic conditions compared to normoxic conditions, suggesting better internalization of the nanoparticles into cancer cells under hypoxia. Fluorescent-dye labeled BSA-CDF-ATZ revealed higher cell uptake of the nanoparticle compared to free dye indicative of better delivery, substantiated by a high rate of apoptosis-mediated cell death compared to free CDF. The significantly higher tumor accumulation and low liver and spleen uptake in TNBC patient-derived tumor xenograft models confirm the significant potential of BSA-CDF-ATZ for targeted TNBC imaging and therapy.

Nowadays, the infection caused by the methicillin-resistant Staphylococcus aureus (MRSA) and countless different types of bacterial infection cause the death of millions of people worldwide. Thereby, several strategies have explored for the advancement of better and active antimicrobial agents; one of these lies in the form of two-dimensional carbon-based nanocomposites. Herein, we demonstrate the synthesis of the graphene–polyindole (Gr@PIn) nanocomposite and polyindole (PIn) and significantly enhance the proficiency against MRSA strains which are immune to most antibiotics. The synthesized Gr@PIn and PIn have been characterized by the various biophysical techniques, especially X-ray diffraction (XRD), electron microscopy [scanning electron microscopy (SEM) and transmission electron microscopy (TEM)], Fourier transform infrared, Raman, UV–vis spectroscopy, and thermogravimetric analysis. Electron microscopic investigations unveiled the disintegration of bacterial cell wall upon interaction with Gr@PIn. S...

A series of steroidal oxazole and thiazole derivatives have been synthesized employing thiosemicarbazide/semicarbazide hydrochloride and ethyl 2-chloroacetoacetate with a simple and facile one-pot multicomponent reaction pathway. The antimicrobial activity of newly synthesized compounds were evaluated against four bacterial strains namely Gram-negative (Escherichia coliand Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) in addition to pathogenic fungi (Candida albicans and Cryptococcus neoformans). Bioactivity assay manifested that most of the compounds exhibited good antimicrobial activity. To provide additional insight into antimicrobial activity, the compounds were also tested for their antibiofilm activity against S. aureus biofilm. Moreover, molecular docking study shows binding of compounds with amino acid residues of DNA gyrase and glucosamine-6-phosphate synthase (promising antimicrobial target) through hydrogen bonding interactions. Hemolytic activity have been also investigated to ascertain the effect of compounds over RBC lysis and results indicate good prospects for biocompatibility. The expedient synthesis of steroidal heterocycles, effective antibacterial and antifungal behavior against various clinically relevant human pathogens, promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents.

microRNAs (miRNAs) are small non-coding RNA transcripts (20–24 nucleotides) that bind to their complementary sequences in the 3′-untranslated regions (3′-UTR) of targeted genes to negatively or positively regulate their expression. miRNAs affect the expression of genes in cells, thereby contributing to several important biological processes, including tumorigenesis. Identifying the miRNA cluster as a human embryonic stem cell (hESC)-specific miRNAs initially led to the identification of miR-371, miR-372, miR-373, and miR-373*, which can ultimately be translated into mature miRNAs. Recent evidence suggests that miR-371–373 genes are abnormally expressed in various cancers and act either as oncogenes or tumor suppressors, indicating they may be suitable as molecular biomarkers for cancer diagnosis and prevention. In this article, we summarize recent studies linking miR-371–373 functions to tumorigenesis and speculate on the potential applications of miR-371–373 as biomarkers for cancer diagnosis and treatment.

Antibodies occupy a central position when it comes to binding proteins with desired antigenic specificities. During the past decade, a plethora of recombinant or humanized versions of antibodies have entered clinical settings with outstanding accomplishments. Yet, they suffer from several drawbacks such as high molecular weight, limited tissue penetration, instability, high production cost, requirement for large doses and potential cytotoxicity. As a result, new generation of receptor proteins has been developed, that are derived from small and robust immunoglobulin (Ig) or non-immunoglobulin based "scaffolds". Combinatorial protein engineering has tremendous scope in the development of these protein scaffolds with immunoglobulin like specificity and/or prescribed binding functions. The advancement made in this regard can boast of developing various validated Ig based and non-Ig protein scaffolds with desirable therapeutic potential. The newly emerging technology has profound scope in translational biology and offer matching replacement for existing immunotherapeutic agents. Only few data from early clinical studies are available yet, but many more are likely to come in the near future. Here, we provide a glimpse of recent clinical advances in the field of existing protein scaffolds.

In the present study, we explored the antibacterial potential of ZnO–nanoparticles that were biomimetically synthesized employing conditioned culture supernatant of Staphylococcus aureus (S. aureus). The in situ synthesized ZnO–NPs were characterized employing various biophysical techniques including UV-vis spectroscopy, electron microscopy, DLS and XRD analysis etc. Electron microscopic studies revealed the disintegration of bacterial cell wall upon interaction with synthesized ZnO–NPs. Various employed tests provided evidence that synthesized ZnO–NPs effectively inhibited less susceptible Gram-positive and Gram-negative bacterial isolates. Moreover, the synthesized ZnO–NPs inhibited the biofilm synthesis of tested microbes in vitro. Finally, the biomimetically synthesized ZnO–NPs successfully treated the S. aureus mediated experimental skin infection in BALB/c mice as well.

Considering the significance of biological and eco-friendly nanomaterials, in the present study, we have synthesized silver nanoparticles from the exopolysaccharide of recently recovered bacterial strain CEES51 from the Red Sea coastal area of Jeddah, Saudi Arabia. 16S ribosomal RNA gene sequencing was used to characterize the isolated bacteria, and it was identified as Mesoflavibacter zeaxanthinifaciens and assigned an accession number {"type":"entrez-nucleotide","attrs":{"text":"MH707257.1","term_id":"1440885400","term_text":"MH707257.1"}}MH707257.1 GenBank. The bacterial strain is an excellent exopolysaccharide producer and survived at hypersaline (30%) and high-temperature (50°C) conditions. The bacterial exopolysaccharides were employed for the fabrication of silver nanoparticles at room temperature. UV-visible spectrophotometer optimized the synthesized nanoparticles, and their size was determined by Nanophox particle size analyzer and dynamic light scattering. Additionally, the X-ray powder diffraction and Fourier-transform infrared spectroscopy studies also approved its crystalline nature and the involvement of organic functional groups in their formation. The synthesized nanomaterials were tested for their antibacterial and antibiofilm properties against pathogenic microorganisms Bacillus subtilis and methicillin-resistant Staphylococcus aureus. The antimicrobial property showed time, and dose-dependent response with a maximum of zone inhibition was observed at around 22 and 18 mm at a dose of 50 µg/well against B. subtilis and S. aureus and a minimum inhibitory concentration of 8 and 10 µg/ml, respectively. Furthermore, the synthesized silver nanoparticles possessed a substantial antibiofilm property and were also found to be biocompatible as depicted by red blood cell lysis assay and their interaction with peripheral blood mononuclear cells and human embryonic kidney 293 cells. Therefore, Mesoflavibacter zeaxanthinifaciens is found to be an excellent source for exopolysaccharide synthesis that assists in the silver nanoparticle production.