Confronting antibiotic-resistant pathogens: Distinctive drug delivery potentials of progressive nanoparticles.

Antimicrobial resistance arises over time, usually due to genetic modifications. Global observations of high resistance rates to popular antibiotics used to treat common bacterial diseases, such as diarrhea, STIs, sepsis, and urinary tract infections, indicate that our supply of effective antibiotics is running low. The mechanisms of action of several antibiotic groups are covered in this review. Antimicrobials disrupt the development and metabolism of bacteria, leading to their eventual death. However, in recent years, microorganisms become resistant to the drugs. Bacteria encode resistant genes against antibiotics and inhibit the function of antibiotics by reducing the uptake of drugs, modifying the enzyme's active site, synthesizing enzymes to degrade antibiotics, and changing the structure of ribosomal subunits. Additionally, the methods of action of resistant bacteria against different kinds of antibiotics as well as their modes of action are discussed. Besides, the resistant pathogenic bacteria which get the most priority by World Health Organisation (WHO) for synthesizing new drugs, have also been incorporated. To overcome antimicrobial resistance, nanomaterials are used to increase the efficacy of antimicrobial drugs. Metallic, inorganic, and polymer-based nanoparticles once conjugated with antibacterial drugs, exhibit synergistic effects by increasing the efficacy of the drugs by inhibiting bacterial growth. Nanomaterial's toxic properties are proportional to their concentrations. Higher concentration nanomaterials are more toxic to the cells. In this review, the toxic properties of nanomaterials on lung cells, lymph nodes, and neuronal cells are also summarized.

An insight into the state of nanotechnology-based electrochemical biosensors for PCOS detection.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting many women of reproductive age all over the world. PCOS is associated with the onset of enduring health complications, notably diabetes and cardiovascular diseases. Furthermore, PCOS escalates the propensity for conditions such as obesity, insulin resistance, and dyslipidemia, which can potentially culminate in life-threatening scenarios. A pervasive predicament surrounding PCOS pertains to its underdiagnosis due to discrepancies in diagnostic criteria and the intricacy of available testing methodologies. Consequently, many women encounter substantial delays in diagnosis with traditional diagnostic approaches. Prompt identification is imperative, as any delay can precipitate severe consequences. The conventional techniques employed for PCOS detection typically suffer from suboptimal accuracy, protracted assay times, and inherent limitations, thereby constraining their widespread applicability and accessibility. In response to these challenges, various electrochemical methods leveraging nanotechnology have been documented. In this concise review, we endeavor to delineate the deficiencies associated with established conventional methodologies while accentuating the distinctive attributes and benefits inherent to contemporary biosensors. We place particular emphasis on elucidating the pivotal advancements and recent breakthroughs in the realm of nanotechnology-facilitated biosensors for the detection of PCOS.

Recent advances in antimicrobial peptide-based therapy.

Antimicrobial peptides (AMPs) are a group of polypeptide chains that have the property to target and kill a myriad of microbial organisms including viruses, bacteria, protists, etc. The first discovered AMP was named gramicidin, an extract of aerobic soil bacteria. Further studies discovered that these peptides are present not only in prokaryotes but in eukaryotes as well. They play a vital role in human innate immunity and wound repair. Consequently, they have maintained a high level of intrigue among scientists in the field of immunology, especially so with the rise of antibiotic-resistant pathogens decreasing the reliability of antibiotics in healthcare. While AMPs have promising potential to substitute for common antibiotics, their use as effective replacements is barred by certain limitations. First, they have the potential to be cytotoxic to human cells. Second, they are unstable in the blood due to action by various proteolytic agents and ions that cause their degradation. This review provides an overview of the mechanism of AMPs, their limitations, and developments in recent years that provide techniques to overcome those limitations. We also discuss the advantages and drawbacks of AMPs as a replacement for antibiotics as compared to other alternatives such as synthetically modified bacteriophages, traditional medicine, and probiotics.

An ultrasensitive electrochemical DNA biosensor for monitoring Human papillomavirus-16 (HPV-16) using graphene oxide/Ag/Au nano-biohybrids.

A DNA-based electrochemical biosensor has been developed herein for the detection of Human papillomavirus-16 (HPV-16). HPV-16 is a double-stranded, non-enveloped, epitheliotropic DNA virus which responsible for cervical cancer. In this proposed biosensor, an indium tin oxide (ITO) coated glass electrode was modified for sensing HPV-16 using graphene oxide and silver coated gold nanoparticles. Subsequently, HPV-16 specific DNA probes were immobilized on a modified ITO surface. The synthesized nanocomposites were characterized by FE-SEM and UV-VIS spectroscopy techniques. Electrochemical characterization was performed by using cyclic voltammetry and electrochemical Impedance Spectroscopy methods. The hybridization between the probe and target DNA was analyzed by a reduction in current, mediated by methylene blue. The biosensor showed a qualitative inequity between the probe and target HPV-16 DNA. The developed biosensor showed high sensitivity as 0.54 mA/aM for the detection of HPV-16. In a linear range of 100 aM to 1 µM with 100 aM LOD, the proposed biosensor exhibited excellent performance with the rapid diagnosis. Thus, the results indicate that the developed HPV DNA biosensor shows good consistency with the present approaches and opens new opportunities for developing point-of-care devices. The diagnosis of HPV-16 infection in its early stage may also be possible with this detection system.

A systematic review on SARS-CoV-2-associated fungal coinfections.

A severe pandemic of Coronavirus Disease (COVID-19) has been sweeping the globe since 2019, and this time, it did not stop, with frequent mutations transforming into virulent strains, for instance, B.1.1.7, B.1.351, and B.1.427. In recent months, a fungal infection, mucormycosis has emerged with more fatal responses and significantly increased mortality rate. To measure the severity and potential alternative approaches against black fungus coinfection in COVID-19 patients, PubMed, Google Scholar, World Health Organization (WHO) newsletters, and other online resources, based on the cases reported and retrospective observational analysis were searched from the years 2015-2021. The studies reporting mucormycosis with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coinfection and/or demonstrating potential risk factors, such as a history of diabetes mellitus or suppressed immune system were included, and reports published in non-English language were excluded. More than 20 case reports and observational studies on black fungus coinfection in COVID-19 patients were eligible for inclusion. The results indicated that diabetes mellitus, hyperglycemic, and immunocompromised COVID-19 patients with mucormycosis were at a higher risk. We found that it was prudent to assess the potential risk factors and severity of invasive mycosis via standardized diagnostic and clinical settings. Large-scale studies need to be conducted to identify early biomarkers and optimization of diagnostic methods has to be established per population and geographical variation. This will not only help clinicians around the world to detect the coinfection in time but also will prepare them for future outbreaks of other potential pandemics.

Interpretative immune targets and contemporary position for vaccine development against SARS-CoV-2: A systematic review.

The year 2020 started with the emergence of novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19 infection. Soon after the first evidence was reported in Wuhan, China, the World Health Organization declared global public health emergency and imminent need to understand the pathogenicity of the virus was required in limited time. Once the genome sequence of the virus was delineated, scientists across the world started working on the development of vaccines. Although, some laboratories have been using previously developed vaccine platforms from severe acute respiratory syndrome coronavirus (SARS) and middle east respiratory syndrome-related coronavirus and apply them in COVID-19 vaccines due to genetic similarities between coronaviruses. We have conducted a literature review to assess the background and current status of COVID-19 vaccines. The worldwide implementation and strategies for COVID-19 vaccine development are summarized from studies reported in years 2015-2020. While discussing the vaccine candidates, we have also explained interpretative immune responses of SARS-CoV-2 infection. There are several vaccine candidates at preclinical and clinical stages; however, only 42 vaccines are under clinical trials. Therefore, more industry collaborations and financial supports to COVID-19 studies are needed for mass-scale vaccine development. To develop effective vaccine platforms against SARS-CoV-2, the genetic resemblance with other coronaviruses are being evaluated which may further promote fast-track trials on previously developed SARS-CoV vaccines.

Advances in diagnosis of Helicobacter pylori through biosensors: Point of care devices.

Invasive as well as non-invasive conventional techniques for the detection of Helicobacter pylori (H. pylori) have several limitations that are being overcome by the development of novel, rapid and reliable biosensors. Herein, we describe several biosensors fabricated for the detection of H. pylori. This review aims to provide the principles of biosensors and their components including in the context to H. pylori detection. The major biorecognition elements in H. pylori detection include antigen/antibodies, oligonucleotides and enzymes. Furthermore, the review describes the transducers, such as electrochemical, optical and piezoelectric, also including microfluidics approaches. An overview of the biomarkers associated with H. pylori pathogenesis is also discussed. Finally, the prospects of advancement and commercialization of point-of-care tools are summarized.

Helicobacter pylori induced reactive oxygen Species: A new and developing platform for detection.

BACKGROUND: Gastric cancer is the third leading cause of cancer-related deaths worldwide. Approximately 70% of cases are caused by a microaerophilic gram-negative bacteria, Helicobacter pylori (H. pylori), which potentially infect almost 50% of world's population. H. pylori is mainly responsible for persistent oxidative stress in stomach and induction of chronic immune responses which ultimately result into DNA damage that eventually can lead to gastric cancer. Oxidative stress is the result of excessive release of ROS/RNS by activated neutrophils whereas bacteria itself also produce ROS in host cells. Therefore, ROS detection is an important factor for development of new strategies related to identification of H. pylori infection. METHODS: The review summarizes the various available techniques for ROS detection with their advantages, disadvantages, and limitations. All of the information included in this review have been retrieved from published studies on ROS generation and its detection methods. RESULTS: Precisely, 71 articles have been incorporated and evaluated for this review. The studied articles were divided into two major categories including articles on H. pylori-related pathogenesis and various ROS detection methods for example probe-based methods, immunoassays, gene expression profiling, and other techniques. The major part of probe activity is based on fluorescence, chemiluminescence, or bioluminescence and detected by complementary techniques such as LC-MS, HPLC, EPR, and redox blotting. CONCLUSION: The review describes the methods for ROS detection but due to some limitations in conventional methods, there is a need of cost-effective, early and fast detection methods like biosensors to diagnose the infection at its initial stage.

Enzyme-based sensing on nanohybrid film coated over FTO electrode for highly sensitive detection of antibiotics.

Cefepime and Meropenem are the new class of antibiotics, which are particularly used as last potent defender or the antibiotics of the last resort against multi-resistant bacterial species. In this paper, an impedance-based electrochemical biosensor was fabricated for identifying antibiotics of last resort in the forensic samples including gastric lavage and other body fluids. The sensor was developed using platinum nanoparticles (PtNPs) and electrodeposited zinc oxide- zinc hexacyanoferrate hybrid film (ZnO/ZnHCF) on the surface of a fluorine-doped glass electrode (FTO). Further, penicillinase was immobilized onto the modified electrode using penicillinase enzyme. The developed biosensor exhibits a good analytical response for the detection of antibiotics evaluated using electrochemistry studies. The linear response of the fabricated electrode was observed from 0.1 to 750 µM and the electrode limit of detection (LOD) was observed as 0.1 µM. The sensor confirms good accuracy, is highly selective, and sensitive for the target. While storing the modified electrode at 4 °C, the stability of biosensor was evaluated for 45 days, and activity loss of 30-40% was observed. The highly sensitive interface of Penicillinase@CHIT/PtNP-ZnO/ZnHCF/FTO electrode shows a promising future in forensic studies.

Triple-nanostructuring-based noninvasive electro-immune sensing of CagA toxin for Helicobacter pylori detection.

BACKGROUND: Helicobacter pylori (H pylori) is gram-negative, spiral, and microaerophilic bacteria which can survive in ~2%-10% oxygen level. It was reported to populate in human gastric mucosa and leads to gastric cancer without any age or gender difference. MATERIALS AND METHODS: In this study, we are targeting label-free electrochemical immunosensor development for rapid H pylori detection after covalently immobilizing the antibody (CagA) over the nanomaterials modified Au electrode. Titanium oxide nanoparticles (TiO2 NPs), carboxylated multi-walled carbon nanotubes (c-MWCNT), and conducting polymer polyindole carboxylic acid (Pin5COOH) composites (TiO2 NPs/c-MWCNT/Pin5COOH) were synthesized and further utilized in immunosensor development as an electrochemical interface onto Au electrode. The stepwise modifications of CagAantibody/TiO2 NPs/c-MWNCT/Pin5COOH/Au electrode were electrochemically studied. RESULTS: Possessing the unique features of advanced materials, the proposed immunosensor reported low sensing limit of 0.1 ng/mL in dynamic linear range of 0.1-8.0 ng/mL with higher stability and reproducibility. Furthermore, developed sensor-based determination of H pylori in five human stool specimens has shown good results with suitable accuracy. CONCLUSIONS: This work lays strong foundation toward developing nanotechnology-enabled electrochemical sensor for ultrasensitive and early detection of H pylori in noninvasively collected clinical samples.

Deep pool water-impacts of viscous oil droplets.

We experimentally study the impacts of viscous, immiscible oil drops into a deep pool of water. Within the target liquid pool, the impacting drop creates a crater, whose dynamics are studied. It is found that the inertia of pool liquid and drop viscosity are the main factors that determine the crater's maximum depth, while the additional factor of mutual immiscibility between the drop and pool liquids leads to interesting interfacial dynamics along the oil-water interface. We discuss how this can change the crater dynamics in its retraction phase, making possible a type of double-entrainment, whereby a tiny air bubble is entrapped inside a water-entrained oil drop. Further, we report the observation of a type of 'fingering' that occurs along the oil-drop rim, which we discuss, arises as a remnant of the well-known crown-splash instability.

Helicobacter pylori VacA, a distinct toxin exerts diverse functionalities in numerous cells: An overview.

BACKGROUND: Helicobacter pylori, gastric cancer-causing bacteria, survive in their gastric environment of more than 50% of the world population. The presence of H. pylori in the gastric vicinity promotes the development of various diseases including peptic ulcer and gastric carcinoma. H. pylori produce and secret Vacuolating cytotoxin A (VacA), a major toxin facilitating the bacteria against the host defense system. The toxin causes multiple effects in epithelial cells and immune cells, especially T cells, B cells, and Macrophages. METHODS: This review describes the diverse functionalities of protein toxin VacA. The specific objective of this review is to address the overall structure, mechanism, and functions of VacA in various cell types. The recent advancements are summarized and discussed and thus conclusion is drawn based on the overall reported evidences. RESULTS: The searched articles on H. pylori VacA were evaluated and limited up to 66 articles for this review. The articles were divided into four major categories including articles on vacA gene, VacA toxin, distinct effects of VacA toxin, and their effects on various cells. Based on these studies, the review article was prepared. CONCLUSIONS: This review describes an overview of how VacA is secreted by H. pylori and contributes to colonization and virulence in multiple ways by affecting epithelial cells, T cells, Dendritic cells, B cells, and Macrophages. The reported evidence suggests that the comprehensive outlook need to be developed for understanding distinctive functionalities of VacA.

Potential biomarkers for effective screening of neonatal sepsis infections: An overview.

Neonatal sepsis, a clinical disorder developed by bacterial blood stream infections (BSI) in neonates, is one of the serious global public health problems that must be addressed. More than one million of the estimated global newborn deaths per year are occurred due to severe infections. The genesis of the infection is divided into early-onset sepsis (EOS) and late-onset sepsis (LOS) of the disease. The clinical complications of neonatal sepsis may be associated with bronchopulmonary dysplasia, ductus arteriosus and necrotizing enterocolitis. The clinical diagnosis and treatment of neonatal sepsis is highly complicated. Over the past few years distinct biomarkers have been identified. Most widely used biomarkers are C-reactive protein, Procalcitonin (PCT) and Serum amyloid A (SAA). Until recently, many potential biomarkers including Cell Surface antigens and Bacterial surface antigens and genetic biomarkers are being investigated. Protein biomarkers, cytokines and chemokines are getting much interest for identification of neonatal sepsis infection.

Characterization of Helicobacter pylori VacA-containing vacuoles (VCVs), VacA intracellular trafficking and interference with calcium signalling in T lymphocytes.

The human pathogen Helicobacter pylori colonizes half of the global population. Residing at the stomach epithelium, it contributes to the development of diseases such as gastritis, duodenal and gastric ulcers, and gastric cancer. A major factor is the secreted vacuolating toxin VacA, which forms anion-selective channels in the endosome membrane that cause the compartment to swell, but the composition and purpose of the resulting VacA-containing vacuoles (VCVs) are still unknown. VacA exerts influence on the host immune response in various ways, including inhibition of T-cell activation and proliferation and suppression of the host immune response. In this study, for the first time the composition of VCVs from T cells was comprehensively analysed to investigate VCV function. VCVs were successfully isolated via immunomagnetic separation, and the purified vacuoles were analysed by mass spectrometry. We detected a set of 122 VCV-specific proteins implicated among others in immune response, cell death and cellular signalling processes, all of which VacA is known to influence. One of the individual proteins studied further was stromal interaction molecule (STIM1), a calcium sensor residing in the endoplasmic reticulum (ER) that is important in store-operated calcium entry. Live cell imaging microscopy data demonstrated colocalization of VacA with STIM1 in the ER and indicated that VacA may interfere with the movement of STIM1 towards the plasma membrane-localized calcium release activated calcium channel protein ORAI1 in response to Ca(2+) store depletion. Furthermore, VacA inhibited the increase of cytosolic-free Ca(2+) in the Jurkat E6-1 T-cell line and human CD4(+) T cells. The presence of VacA in the ER and its trafficking to the Golgi apparatus was confirmed in HeLa cells, identifying these two cellular compartments as novel VacA target structures.

Highly sensitive and rapid detection of acetylcholine using an ITO plate modified with platinum-graphene nanoparticles.

Determining the concentrations of acetylcholine (ACh) and choline (Ch) is clinically important. ACh is a neurotransmitter that acts as a key link in the communication between neurons in the spinal cord and in nerve skeletal junctions in vertebrates, and plays an important role in transmitting signals in the brain. A bienzymatic sensor for the detection of ACh was prepared by co-immobilizing choline oxidase (ChO) and acetylcholinesterase (AChE) on graphene matrix/platinum nanoparticles, and then electrodepositing them on an ITO-coated glass plate. Graphene nanoparticles were decorated with platinum nanoparticles and were electrodeposited on a modified ITO-coated glass plate to form a modified electrode. The modified electrode was characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) studies. The optimum response of the enzyme electrode was obtained at pH 7.0 and 35 °C. The response time of this ACh-sensing system was shown to be 4 s. The linear range of responses to ACh was 0.005-700 µM. This biosensor exhibits excellent anti-interferential abilities and good stability, retaining 50% of its original current even after 4 months. It has been applied for the detection of ACh levels in human serum samples.

Advanced biosensors for nanomaterial-based detection of transforming growth factor alpha and beta, a class of major polypeptide regulators.

Transforming growth factors (TGFs) regulate several cellular processes including, differentiation, growth, migration, extracellular matrix production, and apoptosis. TGF alpha (TGF-α) is a heterogeneous molecule containing 160 amino acid residues. It is a potent angiogenesis promoter that is activated by JAK-STAT signaling. Whereas TGF beta (TGF-ß) consists of 390-412 amino acids. Smad and non-Smad signaling both occur in TGF beta. It is linked to immune cell activation, differentiation, and proliferation. It also triggers pre-apoptotic responses and inhibits cell proliferation. Both growth factors have a promising role in the development and homeostasis of tissues. Defects such as autoimmune diseases and cancer develop mechanisms to modulate checkpoints of the immune system resulting in altered growth factors profile. An accurate amount of these growth factors is essential for normal functioning, but an exceed or fall behind the normal level is alarming as it is linked to several disorders. This demands techniques for TGF-α and TGF-ß profiling to effectively diagnose diseases, monitor their progression, and assess the efficacy of immunotherapeutic drugs. Quantitative detection techniques including the emergence of biosensing technology seem to accomplish the purpose. Until the present time, few biosensors have been designed in the context of TGF-α and TGF-ß for disease detection, analyzing receptor binding, and interaction with carriers. In this paper, we have reviewed the physiology of transforming growth factor alpha and beta, including the types, structure, function, latent/active forms, signaling, and defects caused. It involves the description of biosensors on TGF-α and TGF-ß, advances in technology, and future perspectives.

Ti3C2 (MXene), an advanced carrier system: role in photothermal, photoacoustic, enhanced drugs delivery and biological activity in cancer therapy.

In the realm of healthcare and the advancing field of medical sciences, the development of efficient drug delivery systems become an immense promise to cure several diseases. Despite considerable advancements in drug delivery systems, numerous challenges persist, necessitating further enhancements to optimize patient outcomes. Smart nano-carriers, for instance, 2D sheets nano-carriers are the recently emerging nanosheets that may garner attention for targeted delivery of bioactive compounds, drugs, and genes to kill cancer cells. Within these advancements, Ti3C2TX-MXene, characterized as a two-dimensional transition metal carbide, has surfaced as a prominent intelligent nanocarrier within nanomedicine. Its noteworthy characteristics facilitated it as an ideal nanocarrier for cancer therapy. In recent advancements in drug delivery research, Ti3C2TX-MXene 2D nanocarriers have been designed to release drugs in response to specific stimuli, guided by distinct physicochemical  parameters. This review emphasized the multifaceted role of Ti3C2TX-MXene as a potential carrier for delivering poorly hydrophilic drugs to cancer cells, facilitated by various polymer coatings. Furthermore, beyond drug delivery, this smart nanocarrier demonstrates utility in photoacoustic imaging and photothermal therapy, further highlighting its significant role in cellular mechanisms.

Advances in surface-enhanced Raman spectroscopy-based sensors for detection of various biomarkers.

Surface enhanced Raman spectroscopy (SERS) allows the ultrasensitive detection of analytes present in traces or even single molecule levels by the generation of electromagnetic fields. It is a powerful vibrational spectroscopic method that is capable to detect traces of chemical and biological analytes. SERS technique is involved in the extremely sophisticated studies of molecules with high specificity and sensitivity. In the vicinity of nanomaterials decorated surfaces, SERS can monitor extremely low concentrations of analytes in a non-destructive manner with narrow line widths. This review article is focused on some recently developed SERS-based sensors for distinct types of analytes like disease-related biomarkers, organic and inorganic molecules, various toxins, dyes, pesticides, bacteria as well as single molecules. This study aims to enlighten the arising sensing approaches based on the SERS technique. Apart from this, some basics of the SERS technique like their mechanism, detection strategy, and involvement of some specific nanomaterials are also highlighted herein. Finally, the study concluded with some discussion of applications of SERS in various fields like food and environmental analysis.

Recent progress in biomarker-based diagnostics of Helicobacter pylori, gastric cancer-causing bacteria.

The progression of any disease and its outcomes depend on the complicated interaction between pathogens, host and environmental factors. Thus, complete knowledge of bacterial toxins involved in pathogenesis is necessary to develop diagnostic methods and alternative therapies, including vaccines. This review summarizes recently employed biomarkers to diagnose the presence of Helicobacter pylori bacteria. The authors review distinct types of disease-associated biomarkers such as urease, DNA, miRNA, aptamers and bacteriophages that can be utilized as targets to detect Helicobacter pylori and, moreover, gastric cancer in its early stage. A detailed explanation is also given in the context of the recent utilization of these biomarkers in the development of a highly specific and sensitive biosensing platform.

Advancement in biomarker based effective diagnosis of neonatal sepsis.

Neonatal sepsis is considered as alarming medical emergency and becomes the common global reason of neonatal mortality. Non-specific symptoms and limitations of conventional diagnostic methods for neonatal sepsis mandate fast and reliable method to diagnose disease for point of care application. Recently, disease specific biomarkers have gained interest for rapid diagnosis that led to the development of electrochemical biosensor with enhanced specificity, sensitivity, cost-effectiveness and user-friendliness. Other than conventional biomarker C-reactive protein to diagnose neonatal sepsis, several potential biomarkers including Procalcitonin (PCT), Serum amyloid A (SAA) and other candidates are extensively investigated. The present review provides insights on advancements and diagnostic abilities of protein and nucleotide based biomarkers with their incorporation in developing electrochemical biosensors by employing novel fabrication strategies. This review provides an overview of most promising biomarker and its capability for neonatal sepsis diagnosis to fulfil future demand to develop electrochemical biosensor for point-of-care applications.