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The world is currently dealing with a second viral outbreak, monkeypox, which has the potential to become an epidemic after the COVID-19 pandemic. People who reside in or close to forest might be exposed indirectly or at a low level, resulting in subclinical disease. However, the disease has lately emerged in shipped African wild mice in the United States. Smallpox can cause similar signs and symptoms to monkeypox, such as malaise, fever, flu-like signs, headache, distinctive rash, and back pain. Because Smallpox has been eliminated, similar symptoms in a monkeypox endemic zone should be treated cautiously. Monkeypox is transmitted to humans primarily via interaction with diseased animals. Infection through inoculation via interaction with skin or scratches and mucosal lesions on the animals is conceivable significantly once the skin barrier is disrupted by scratches, bites, or other disturbances or trauma. Even though it is clinically unclear from other pox-like infections, laboratory diagnosis is essential. There is no approved treatment for human monkeypox virus infection, however, smallpox vaccination can defend counter to the disease. Human sensitivity to monkeypox virus infection has grown after mass vaccination was discontinued in the 1980s. Infection may be prevented by reducing interaction with sick patients or animals and reducing respiratory exposure among people who are infected.

Abstract 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.

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.

Objectives: The Asian swamp eel (Monopterus albus), is commonly distributed in Asian countries. However, its therapeutic potential has not been thoroughly investigated yet. The current study aimed to evaluate the in-vivo therapeutic properties of the skin mucus of this fish. Methods: The eel mucus was collected fleshly and topical gel with carbopol 934 was formulated to study the antibacterial activity on the infected skin of the rats. Sprague Dawley rats were used in the study and divided into 4 groups negative, positive, normal control, and treated groups. Results: Intracutaneous injections of pathogenic bacteria (Streptococcus pyogenes, Staphylococcus aureus) and fungi (Microsporum gypseum, Candida albicans) were injected into the rats. The development of tinea capitis, impetigo, and cutaneous candidiasis in the animal model was confirmed based on clinical and histopathological observations. To treat the infected rats, a formulated gel of eel skin mucus was applied on the infected rat’s skins topically. The histological analysis confirms a complete recovery in the skin tissues similar to commercial antifungal and antibacterial agents used in the positive control groups. Conclusion: The present novel eel skin mucus is an efficient therapeutic candidate in treating skin infections associated with pathogenic microbes.

In this research, Bougainvillea glabra paper flower extract was used to quickly synthesize biogenic silver nanoparticles (BAgNPs) utilizing green chemistry. Using the flower extract as a biological reducing agent, silver nanoparticles were generated by the conversion of Ag+ cations to Ag0 ions. Data patterns obtained from physical techniques for characterizing BAgNPs, employing UV-visible, scattering electron microscope (SEM), transmission electron microscope (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR), suggested that the nanoparticles have a spherical to oval form with size ranging from 10 to 50 nm. Spectroscopy and microscopic analysis were used to learn more about the antibacterial properties of the biologically produced BAgNPs from Bougainvillea glabra. Further, the potential mechanism of action of nanoparticles was investigated by studying their interactions in vitro with several bacterial strains and mammalian cancer cell systems. Finally, we can conclude that BAgNPs can be functionalized to dramatically inhibit bacterial growth and the growth of cancer cells in culture conditions, suggesting that biologically produced nanomaterials will provide new opportunities for a wide range of biomedical applications in the near future.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Nanotechnology-based medicinal approaches deliver valuable cargos targeting molecular and cellular processes with greater safety, efficacy, and specificity than traditional approaches. CNS diseases include a wide range of brain ailments connected to short- and long-term disability. They affect millions of people worldwide and are anticipated to become more common in the coming years. Nanotechnology-based brain therapy could solve the BBB problem. This review analyzes nanomedicine’s role in medication delivery; immunotherapy, chemotherapy, and gene therapy are combined with nanomedicines to treat CNS disorders. We also evaluated nanotechnology-based approaches for CNS disease amelioration, with the intention of stimulating the immune system by delivering medications across the BBB.

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.

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.

Abstract 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.

Plants, being the significant and natural source of medication for humankind against several ailments with characteristic substances hidden on them, have been recognized for many centuries. Accessibility of various methodologies for the revelation of therapeutically characteristic items has opened new avenues to redefine plants as the best reservoirs of new structural types. The role of plant metabolites to hinder the development and movement of pathogenic microbes is cherished. Production of extended-spectrum β-lactamases is an amazing tolerance mechanism that hinders the antibacterial treatment of infections caused by Gram-negative bacteria and is a serious problem for the current antimicrobial compounds. The exploration of the invention from sources of plant metabolites gives sustenance against the concern of the development of resistant pathogens. Essential oils are volatile, natural, complex compounds described by a solid odor and are framed by aromatic plants as secondary metabolites. The bioactive properties of essential oils are commonly controlled by the characteristic compounds present in them. They have been commonly utilized for bactericidal, virucidal, fungicidal, antiparasitic, insecticidal, medicinal, and antioxidant applications. Alkaloids are plant secondary metabolites that have appeared to have strong pharmacological properties. The impact of alkaloids from Callistemon citrinus and Vernonia adoensis leaves on bacterial development and efflux pump activity was assessed on Pseudomonas aeruginosa. Plant-derived chemicals may have direct antibacterial activity and/or indirect antibacterial activity as antibiotic resistance modifying agents, increasing the efficiency of antibiotics when used in combination. The thorough screening of plant-derived bioactive chemicals as resistance-modifying agents, including those that can act synergistically with antibiotics, is a viable method to overcome bacterial resistance. The synergistic assessment studies with the plant extract/essential oil and the antibiotic compounds is essential with a target for achieving a redesigned model with sustainable effects which are appreciably noticeable in specific sites of the plants compared to the entirety of their individual parts.

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.

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.

Abstract Biomimetic synthesis of nanoparticles offers a convenient and bio friendly approach to fabricate complex structures with sub-nanometer precision from simple precursor components. In the present study, we have synthesized nanoparticles of Amphotericin B (AmB), a potent antifungal agent, using Aloe vera leaf extract. The synthesis of AmB nano-assemblies (AmB-NAs) was established employing spectro-photometric and electron microscopic studies, while their crystalline nature was established by X-ray diffraction. AmB-nano-formulation showed much higher stability in both phosphate buffer saline and serum and exhibit sustained release of parent drug over an extended time period. The as-synthesized AmB-NA possessed significantly less haemolysis as well as nephrotoxicity in the host at par with Ambisome®, a liposomized AmB formulation. Interestingly, the AmB-NAs were more effective in killing various fungal pathogens including Candida spp. and evoked less drug related toxic manifestations in the host as compared to free form of the drug. The data of the present study suggest that biomimetically synthesized AmB-NA circumvent toxicity issues and offer a promising approach to eliminate systemic fungal infections in Balb/C mice.

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 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.

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.

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.

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.

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.

Triple-negative breast cancer (TNBC) is amongst the most challenging tumor subtypes because it presents itself without the estrogen, progesterone, and HER2 receptors. Hence, assessing new markers is an essential requirement for enhancing its targeted treatment. The survival of TNBC relies upon the advancement of hypoxia that contributes to treatment resistance, immune response resistance, and tumor stroma arrangement. Here, we explored bovine serum albumin (BSA) nanoparticle encapsulating the anti-cancer drug Paclitaxel (PTX) for cell-killing mediated by tumor hypoxia. For targeting hypoxia, we conjugated Acetazolamide (ATZ) with BSA nanoparticle that encapsulated PTX (referred hereon as BSA-PTX-ATZ) utilizing copper-free click chemistry, specifically the Strain-Promoted Alkyne Azide Cycloaddition (SPAAC). The in-vitro cell killing study uncovered that BSA-PTX-ATZ is more productive contrasted with free PTX. The evaluations of the physio-chemical properties of BSA-PTX-ATZ proves that the shelf-life is approximately two months when stored either at room or freezing temperatures or under refrigerated conditions. There is no leakage of PTX from the formulation during that period, while their nanoparticulate nature remained undisturbed. The BSA-PTX-ATZ nanoparticles indicated altogether higher cell killing in hypoxic conditions contrasted with normoxia proposing the hypoxia-mediated delivery mechanism of the activity of the formulation. Higher cell uptake found with fluorescent-marked BSA-PTX-ATZ shows CA-IX mediated cell uptake, substantiated by the prominent apoptotic cell death contrasted with free PTX.

In general, the members of Lip gene family of Mycobacterium tuberculosis evoke strong immune response in the host. Keeping this fact into consideration, we investigated role of Rv3203, a cell wall associated protein with lipolytic activity, in imparting protection against experimental murine tuberculosis. The data of the present study suggested that archaeosome encapsulated Rv3203 induce strong lymphocyte proliferation, up-regulated Th-1 biased cytokines profile, increased expression of co-stimulatory markers on both antigen presenting cells and T lymphocytes. The immuno-prophylactic response was further modulated by exposure of the animals to zymosan, a TLR2/6 agonist, prior to immunization with archaeosome encapsulated Rv3203. Interestingly, pre-treatment of experimental animals with zymosan boosted strong immunological memory as compared to archaeosome encapsulated Rv3203 as well as BCG vaccine. We conclude that priming of immunized animal with TLR agonist followed by immunization with archaeosomes encapsulated Rv3203 offer substantial protection against tuberculosis infection and could be a potential subunit vaccine based prophylactic strategy.