Emerging trends and future challenges of advanced 2D nanomaterials for combating bacterial resistance.

The number of multi-drug-resistant bacteria has increased over the last few decades, which has caused a detrimental impact on public health worldwide. In resolving antibiotic resistance development among different bacterial communities, new antimicrobial agents and nanoparticle-based strategies need to be designed foreseeing the slow discovery of new functioning antibiotics. Advanced research studies have revealed the significant disinfection potential of two-dimensional nanomaterials (2D NMs) to be severed as effective antibacterial agents due to their unique physicochemical properties. This review covers the current research progress of 2D NMs-based antibacterial strategies based on an inclusive explanation of 2D NMs' impact as antibacterial agents, including a detailed introduction to each possible well-known antibacterial mechanism. The impact of the physicochemical properties of 2D NMs on their antibacterial activities has been deliberated while explaining the toxic effects of 2D NMs and discussing their biomedical significance, dysbiosis, and cellular nanotoxicity. Adding to the challenges, we also discussed the major issues regarding the current quality and availability of nanotoxicity data. However, smart advancements are required to fabricate biocompatible 2D antibacterial NMs and exploit their potential to combat bacterial resistance clinically.

Self-assembled and Zn(II)-coordinated dipeptide nanoparticles with membrane-rupturing action on bacteria.

Metal ion-coordinated self-assembled short-chain amino acid peptide molecules with multi-photon excitation wavelengths and their photoluminescence properties are advantageous for fluorescence-based diagnostics and treatments of biological diseases based on their extra features of antibacterial agents. We have designed a novel strategy based on tryptophan molecule coordinated with Zn(II) ions in the form of biocompatible spherical nanoparticles of diameter 30-80 nm which have been used for antibacterial treatments against different kinds of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, and Pseudomonas). Preferably, we have used tryptophan-phenylalanine (Trp-Phe), a dipeptide molecule having tryptophan as principal material against E. coli strains as antimicrobial agents for surface rupturing and killing purposes. Furthermore, based on single amino acid, tryptophan, self-assembled and Zn(II)-coordinated dipeptide nanoparticles (Zn-DPNPs) were studied against three types of multi-drug-resistant bacteria as an active antimicrobial agent. These antibacterial efficient nanoparticles may have best alternative of antibiotic drugs for clinical applications. The capability of self-assembled fluorescence behavior of Zn-coordinated dipeptide molecules and higher hydrophobicity against bacterial cell wall will perform as antimicrobial fluorescent agents. KEY POINTS: • Zn(II) and Cu(II) better coordinated into self-assembled NPs. • Fluorescence signals showed interaction of NPs with gram -ve cell wall. • Significant surface-damaging effects were observed in the case of Cu-DPNPs and Zn-DPNPs.

Copper-based nanoparticles against microbial infections.

Drug-resistant bacteria and highly infectious viruses are among the major global threats affecting the human health. There is an immediate need for novel strategies to tackle this challenge. Copper-based nanoparticles (CBNPs) have exhibited a broad antimicrobial capacity and are receiving increasing attention in this context. In this review, we describe the functionalization of CBNPs, elucidate their antibacterial and antiviral activity as well as applications, and briefly review their toxicity, biodistribution, and persistence. The limitations of the current study and potential solutions are also shortly discussed. The review will guide the rational design of functional nanomaterials for antimicrobial application. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Gold nanocubes based optical detection of HIV-1 DNA via surface enhanced Raman spectroscopy.

Optical detection of HIV-1 DNA with surface enhanced Raman spectroscopy (SERS) is a quick and versatile method, having great potential in screening and characterization of HIV-1 virus particle. We have synthesized and applied novel gold nanocubes (AuNCs) for signal enhancement of SERS to study HIV-1 DNA strands by taking into account the specific vibrational bands of functional groups. Raman peaks at 562 cm-1, 800 cm-1, 1094 cm-1 were observed in both Human Random Control DNA and HIV-1 DNA, while three new peaks were detected in infected DNA at 421 cm-1, 1069 cm-1 and 1254 cm-1. Raman bands in case of AuNCs coated HIV-1 DNA molecules were observed with enhanced intensity values as compared to the silver nanoparticles-based SERS substrate. In case of silver nanoparticles (AgNPs) conjugate DNA, we get all signatures of HIV-1 virus at almost the same position with peak distortions, peak alterations and intensities reductions. We overall molecularly observed HIV-1 infected DNA and Human Random Control DNA, with high sensitivity and selectivity using highly sensitive and stable AuNCs in SERS. This technique can be utilized to identify molecular structures and chemical identification of biomacromolecules which can further be investigated as biomarkers for the screening of whole-body HIV-1 virus particles.

Tailoring bismuth-based nanoparticles for enhanced radiosensitivity in cancer therapy.

Achieving a complete response to cancer treatment is a severe challenge, and has puzzled humans for a long time. Fortunately, radiotherapy (RT) gives rise to a common clinical treatment method, during which the usage of radiosensitizers is essential. Among preclinical radiosensitizers, bismuth-based nanoparticles (Bi-based NPs) are widely explored in cancer diagnosis and treatment, because they share favourable properties, such as low toxicity, strong X-ray absorption and facile preparation. However, pure Bi alone cannot achieve both efficient and safe RT outcomes, mainly due to poor targeting of tumor sites, long retention-induced systemic toxicity and immune resistance. This work provides an overview of recent advances and developments in Bi-based NPs that are tailored to enhance radiosensitivity. For the fabrication process, surface modification of Bi-based NPs is essential to achieve tumor-targeted delivery and penetration. Moreover, the incorporation of other elements, such as Fe ions, can increase diagnostic accuracy with optimal theranostic efficacy. Meanwhile, the structure-activity relationship can also be manipulated to maximize the chemotherapeutic drug loading capability of Bi-based NPs, to enhance X-ray attenuation by means of a large surface area or to achieve safer metabolic routes with rapid clearance from the human body. In addition, Bi-based NPs exhibit synergistic antitumor potential when combined with diverse therapies, such as photothermal therapy (PTT) and high-intensity focused ultrasound (HIFU). To summarize, the latest research on Bi-based NPs as radiosensitizers is described in the review, including both their advantages and disadvantages for improving treatment, thus providing a useful guide for future clinical application.

Engineering carbon nanotubes for sensitive viral detection.

Viral infections have been proven a severe threat to human beings, and the pandemic of Coronavirus Disease 2019 (COVID-19) has become a societal health concern, including mental distress and morbidity. Therefore, the early diagnosis and differentiation of viral infections are the prerequisite for curbing the local and global spread of viruses. To this end, carbon nanotubes (CNTs) based virus detection strategies are developed that provide feasible alternatives to conventional diagnostic techniques. Here in this review, an overview of the design and engineering of CNTs-based sensors for virus detection is summarized, followed by the nano-bio interactions used in developing biosensors. Then, we classify the viral sensors into covalently engineered CNTs, non-covalently engineered CNTs, and size-tunable CNTs arrays for viral detection, based on the type of CNTs-based nano-bio interfaces. Finally, the current challenges and prospects of CNTs-based sensors for virus detection are discussed.

Frequency and risk factors of musculoskeletal disorders in high risk occupation workers in Urban, Karachi.

OBJECTIVE: To determine the frequency and risk factors of musculoskeletal disorders in high-risk occupation workers in an urban setting. METHODS: The analytical cross-sectional study was conducted in Karachi from July to December 2020, and comprised office workers, operation theatre technicians and coolies. The presence of musculoskeletal disorders was assessed using the Nordic Musculoskeletal Questionnaire to determine factors associated with moderate to severe condition. Data was analysed using SPSS 20. RESULTS: Of the 300 male subjects, 100(33.3%) each were office workers, operation theatre technicians and coolies. The overall mean age was 33.25±6.8 years (range: 18-50 years). The overall prevalence of musculoskeletal disorders was 179(59.7%). Besides, 117(65.4%) patients with musculoskeletal disorders had intermediate stage of the disease. The lower back and neck were the most common site of trouble involved in preceding 12 months 111(43.6%) each. CONCLUSIONS: Prevalence of musculoskeletal disorders was found to be a common problem affecting high-risk occupational workers.

Microbes-mediated synthesis strategies of metal nanoparticles and their potential role in cancer therapeutics.

Past few years have seen a paradigm shift towards ecofriendly, green and biological fabrication of metal nanoparticles (MNPs) for diverse nanomedicinal applications especially in cancer nanotheranostics. Besides, the well-known green synthesis methods of plant materials, the potential of the microbial world (bacteria, fungi, alga, etc.) in biofabrication is equally realized. Biomolecules and enzymes in the microbial cells are capable of catalyzing the biosynthesis process. These microbial derived inorganic nanoparticles have been frequently evaluated as potential agents in cancer therapies revealing exciting results. Through, cellular and molecular pathways, these microbial derived nanoparticles are capable of killing the cancer cells. Considering the recent developments in the anticancer applications of microbial derived inorganic MNPs, a dire need was felt to bring the available information to a single document. This manuscript reviews not only the mechanistic aspects of the microbial derived MNPs but also include the diverse mechanisms that governs their anticancer potential. Besides, an updated literature review is presented that includes studies of 2019-onwards.

Psychological impact of COVID-19 Pandemic and associated factors on college students.

OBJECTIVE: To determine the psychological impact of coronavirus disease-2019 pandemic on college students, and to explore factors influencing their anxiety and depression levels. METHODS: The cross-sectional study was conducted from October 2020 to January 2021 at the Jinnah Sindh Medical University, Karachi, and comprised medical students of either gender in the first to third year of the academic programme. Data was collected using a pretested online structured questionnaire comprising demographic information, academic problems, daily life difficulties and the 25-item Aga Khan University Anxiety and Depression Scale. Data was analysed using SPSS22. RESULTS: Of the 397 students, 72(18.1%) were males and 325(81.9%) were females. The overall mean age of the sample was 19.9±1.2 years. Of the total, 221(55.7%) students were found to be anxious and depressed. Factors related to academic difficulties and daily life issues had significant correlation (p<0.05) with anxiety and depression. Multiple linear regression analysis indicated that the need for some form of mental health support was the most significant (p<0.001) predictor of anxiety and depression, followed by family issues (p<0.001) and social media (p<0.001). Anxiety and depression were also significantly associated with fear of family or friend getting coronavirus disease-2019 (p=0.003), lack of attentiveness to study (p=0.040) and felt anxiety when ordering food online (p=0.019). CONCLUSIONS: With better understanding, academic institutions and healthcare policymakers may take measures and mitigate students' distress during the pandemic.

Extraction optimization, Total Phenolic-Flavonoids content, HPLC-DAD finger printing, antimicrobial, antioxidant and cytotoxic potentials of Chinese folklore Ephedra intermedia Schrenk & C. A. Mey

Abstract Plants from genus Ephedra are commonly used by the Chinese people as folk medicine for treatment of various diseases. The current study was designed to explore the ethno-pharmacological based pharmacological potentials of Ephedra intermedia Schrenk & C.A. Mey. (E. intermedia). Plant aerial parts were extracted using ten solvent systems with increasing order of polarity. Samples were analyzed for total phenolic and flavonoid contents, HPLC-DAD analysis, antibacterial, antifungal, HepG2 cell line cytotoxicity, hemolysis and antioxidant potentials following standard procedures. Highest percent extract recovery was observed in Eth+WT (25.55 % w/w) solvent system. Flavonoid and phenolic contents were higher in chloroform and Met+WT fractions respectively. Considerable antibacterial activity was shown by Eth+Met extract against B. subtilis and K. pneumonia (MIC of 11.1μg/mL for each). Eth extract exhibited high antifungal activity against A. fumigates (15±0.31 mm DIZ). Met+WT extract showed significant cytotoxicity against HepG2 cell lines with IC50 of 13.51+0.69 μg/mL. Substantial free radical scavenging activity (74.9%) was observed for Met+Eth extract. In the current study, several solvent systems were used for more effective extraction of fractions and can be useful in the isolation of phytochemicals. Various fractions exhibited considerable antimicrobial, antioxidant and cytotoxic potentials. Biological potentials of E. intermedia signify its potential uses in microbial, cancer and degenerative disorders and thus warrant further detailed studies.

Stimulus-Responsive Smart Nanoparticles-Based CRISPR-Cas Delivery for Therapeutic Genome Editing.

The innovative research in genome editing domains such as CRISPR-Cas technology has enabled genetic engineers to manipulate the genomes of living organisms effectively in order to develop the next generation of therapeutic tools. This technique has started the new era of "genome surgery". Despite these advances, the barriers of CRISPR-Cas9 techniques in clinical applications include efficient delivery of CRISPR/Cas9 and risk of off-target effects. Various types of viral and non-viral vectors are designed to deliver the CRISPR/Cas9 machinery into the desired cell. These methods still suffer difficulties such as immune response, lack of specificity, and efficiency. The extracellular and intracellular environments of cells and tissues differ in pH, redox species, enzyme activity, and light sensitivity. Recently, smart nanoparticles have been synthesized for CRISPR/Cas9 delivery to cells based on endogenous (pH, enzyme, redox specie, ATP) and exogenous (magnetic, ultrasound, temperature, light) stimulus signals. These methodologies can leverage genome editing through biological signals found within disease cells with less off-target effects. Here, we review the recent advances in stimulus-based smart nanoparticles to deliver the CRISPR/Cas9 machinery into the desired cell. This review article will provide extensive information to cautiously utilize smart nanoparticles for basic biomedical applications and therapeutic genome editing.

Review on Recent Progress in Magnetic Nanoparticles: Synthesis, Characterization, and Diverse Applications.

Diverse applications of nanoparticles (NPs) have revolutionized various sectors in society. In the recent decade, particularly magnetic nanoparticles (MNPs) have gained enormous interest owing to their applications in specialized areas such as medicine, cancer theranostics, biosensing, catalysis, agriculture, and the environment. Controlled surface engineering for the design of multi-functional MNPs is vital for achieving desired application. The MNPs have demonstrated great efficacy as thermoelectric materials, imaging agents, drug delivery vehicles, and biosensors. In the present review, first we have briefly discussed main synthetic methods of MNPs, followed by their characterizations and composition. Then we have discussed the potential applications of MNPs in different with representative examples. At the end, we gave an overview on the current challenges and future prospects of MNPs. This comprehensive review not only provides the mechanistic insight into the synthesis, functionalization, and application of MNPs but also outlines the limits and potential prospects.

Tailoring metal-organic frameworks-based nanozymes for bacterial theranostics.

Nanozymes are next-generation artificial enzymes having distinguished features such as cost-effective, enhanced surface area, and high stability. However, limited selectivity and moderate activity of nanozymes in the biochemical environment hindered their usage and encouraged researchers to seek alternative catalytic materials. Recently, metal-organic frameworks (MOFs) characterized by distinct crystalline porous structures with large surface area, tunable pores, and uniformly dispersed active sites emerged, that filled the gap between natural enzymes and nanozymes. Moreover, by selecting suitable metal ions and organic linkers, MOFs can be designed for effective bacterial theranostics. In this review, we briefly presented the design and fabrication of MOFs. Then, we demonstrated the applications of MOFs in bacterial theranostics and their safety considerations. Finally, we proposed the major obstacles and opportunities for further development in research on the interface of nanozymes and MOFs. We expect that MOFs based nanozymes with unique physicochemical and intrinsic enzyme-mimicking properties will gain broad interest in both fundamental research and biomedical applications.

Safety Assessment of Nanomaterials for Antimicrobial Applications.

The interplay between nanotechnology and pathogens offers a new quest to fight against human infections. Inspiring from their unique thermal, magnetic, optical, or redox potentials, numerous nanomaterials have been employed for bacterial theranostics. The past decade has seen dramatic progress in the development of various nanoantimicrobials, which demands more focus on their safety assessment. The present review critically discusses the toxicity of nanoantimicrobials and the role of key features, including composition, size, surface charge, loading capability, hydrophobicity/philicity, precise release, and functionalization, that can contribute to modulating the effects on microbes. Moreover, how differences in microbe's structure, biofilm formation, persistence cells, and intracellular pathogens bestow resistance or sensitivity toward nanoantimicrobials is broadly investigated. In extension, the most important types of nanoantimicrobial with clinical prospective and their safety assessment are summarized, and finally, based on available evidence, an insight of the principles in designing safer nanoantimicrobials for overcoming pathogens and future challenges in the field is provided.

Designing Stimuli-Responsive Upconversion Nanoparticles that Exploit the Tumor Microenvironment.

Tailoring personalized cancer nanomedicines demands detailed understanding of the tumor microenvironment. In recent years, smart upconversion nanoparticles with the ability to exploit the unique characteristics of the tumor microenvironment for precise targeting have been designed. To activate upconversion nanoparticles, various bio-physicochemical characteristics of the tumor microenvironment, namely, acidic pH, redox reactants, and hypoxia, are exploited. Stimuli-responsive upconversion nanoparticles also utilize the excessive presence of adenosine triphosphate (ATP), riboflavin, and Zn2+ in tumors. An overview of the design of stimulus-responsive upconversion nanoparticles that precisely target and respond to tumors via targeting the tumor microenvironment and intracellular signals is provided. Detailed understanding of the tumor microenvironment and the personalized design of upconversion nanoparticles will result in more effective clinical translation.

Recent advances in the analysis of nanoparticle-protein coronas.

In spite of radical advances in nanobiotechnology, the clinical translation of nanoparticle (NP)-based agents is still a major challenge due to various physiological factors that influence their interactions with biological systems. Recent decade witnessed meticulous investigation on protein corona (PC) that is the first surrounds NPs once administered into the body. Formation of PC around NP surface exhibits resilient effects on their circulation, distribution, therapeutic activity, toxicity and other factors. Although enormous literature is available on the role of PC in altering pharmacokinetics and pharmacodynamics of NPs, understanding on its analytical characterization methods still remains shallow. Therefore, the current review summarizes the impact of PC on biological fate of NPs and stressing on analytical methods employed for studying the NP-PC.

Association of Non-Hodgkin lymphoma risk with CYP1A1, GSTM1 and GSTT1 gene variants, in tobacco addicted patients of Pashtun ethnicity of Khyber Pakhtunkhwa, Pakistan.

The current study determines the possible antitumor and immunomodulatory effects of thymosin against the in vivo and in vitro growth of tumor-derived cell line in mice. Peritoneal phagocytes count, Ehrlich ascites tumor (EAT) cells, T- lymphocytes, and B- lymphocytes activities were determined. In addition, serum level of interleukin 2 (IL-2) and liver functions were measured. In animal testing, thymosin at doses of 0.50 and 1mg activated the phagocytic function of macrophages, as well as T- and B- cell function. Thymosin caused a marked shortage in the proliferation of EAT cells in the peritoneal fluid with dose 0.50g as compared with that of the corresponding control group. Furthermore, treatment with thymosin caused effectively elevate in serum level of IL-2, on the contrary reduce in serum levels of ALT, AST and total proteins. The size of solid Ehrlich tumor was significantly decreased, as measured morphologically with the doses 0.50 and 1 mg (P<0.01). These results confirmed that many biological activities attributed to thymosin and is as an adjuvant for immune enhancement.

Neuroprotective Studies on Polygonum hydropiper L. Essential Oils Using Transgenic Animal Models.

Polygonum hydropiper L. and related species are reported to possess neuroprotective potentials. In an attempt to validate its anti-Alzheimer's potentials, leaf oils (Ph. Lo) were extensively evaluated in this study against several in vitro and in vivo models of Alzheimer's disease. The Ph. Lo were tested against pathological targets of Alzheimer's diseases (ADs). The in vitro and in vivo assays were done for cholinesterase inhibition, anti-radical properties and cognitive assessments using transgenic animal models. In preliminary cholinesterase inhibition assays, Ph. Lo were more active against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2) radicals. Subsequently, Ph. Lo was evaluated for its effects on special memory, exploratory behavior, and coordination using shallow water maze (SWM), Y-maze, open filed, and balance beam tests. Animal pre-genotyping was done via polymerase chain reaction (PCR) to confirm amyloid precursor protein (APP) transgene, and after completion of drug therapy, brain homogenates from the cortex and hippocampus were evaluated for cholinesterase and free radical studies. In SWM task, disease control animals treated with 10 mg/kg of Ph. Lo for 5 days exhibited significant improvement in cognitive performance indicated by low escape times on 5th day compared with normal animals. In the Y-maze test, transgenic animals showed higher spontaneous alternation behavior than disease control animals and standard control group animals. Ph. Lo therapy has improved the exploratory behavior and declined anxiety behavior in diseased animals as accessed via open field test. Ph. Lo administration significantly augmented the motor and coordination abilities of transgenic animals when compared to other groups of animals and declined AChE, BChE activities as well as free radicals load in the cortex and hippocampus tissues. Based on our finding, it is concluded that Ph. Lo exhibit significant neuroprotective potentials preliminary due to their anti-radicals and cholinesterase inhibitory activities. Ph. Lo need further detailed studies as potential aromatherapy against neurodegenerative disorders.