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.

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.

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.

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 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.

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.

Fabrication of a Molecularly Imprinted Nano-Interface-Based Electrochemical Biosensor for the Detection of CagA Virulence Factors of H. pylori.

H. pylori is responsible for several stomach-related diseases including gastric cancer. The main virulence factor responsible for its establishment in human gastric cells is known as CagA. Therefore, in this study, we have fabricated a highly sensitive MIP-based electrochemical biosensor for the detection of CagA. For this, an rGO and gold-coated, screen-printed electrode sensing platform was designed to provide a surface for the immobilization of a CagA-specific, molecularly imprinted polymer; then it was characterized electrochemically. Interestingly, molecular dynamics simulations were studied to optimize the MIP prepolymerization system, resulting in a well-matched, optimized molar ratio within the experiment. A low binding energy upon template removal indicates the capability of MIP to recognize the CagA antigen through a strong binding affinity. Under the optimized electrochemical experimental conditions, the fabricated CagA-MIP/Au/rGO@SPE sensor exhibited high sensitivity (0.275 µA ng-1 mL-1) and a very low limit of detection (0.05 ng mL-1) in a linear range of 0.05-50 ng mL-1. The influence of other possible interferents in analytical response has also been observed with the successful determination of the CagA antigen.

Fabrication of a sensing platform for identification of tumor necrosis factor-alpha: a biomarker for neonatal sepsis.

Neonatal sepsis is a prime cause of neonatal deaths across the globe. Presently, various medical tests and biodevices are available in neonatal care. These diagnosis platforms possess several limitations such as being highly expensive, time-consuming, or requiring skilled professionals for operation. These limitations can be overcome through biosensor development. This work discusses the assembling of an electrochemical sensing platform that is designed to detect the level of tumor necrosis factor-alpha (TNF-α). The sensing platform was moderated with nanomaterials molybdenum disulfide nanosheets (MoS2NSs) and silicon dioxide-modified iron oxide nanoparticles (Fe3O4@SiO2NPs). The integration of nanomaterials helps in accomplishing the improved characteristics of the biosensor in terms of conductivity, selectivity, and sensitivity. Further, the molecularly imprinted polymer (MIP) approach was incorporated for sensing the presence of TNF-α on the surface of the working electrode. The electrochemical response of the electrode was recorded at different conditions. A broad concentration range was selected to optimize the biosensor from 0.01 pM to 100 nM. The sensitivity of the biosensor was higher and it exhibits a lower detection limit (0.01 pM).

Emerging vistas on pesticides detection based on electrochemical biosensors - An update.

Organophosphates and carbamates pesticides are widely used to increase crop production globally causing a threat to human health and the environment. A variety of pesticides are applied during different stages of vegetable production. Therefore, monitoring the presence of pesticide residues in food and soil has great relevance to sensitive pesticide detection through distinct determination methods that are urgently required. Conventional techniques for the detection of pesticides have several limitations that can be overcome by the development of highly sensitive, fast, reliable and easy-to-use electrochemical biosensors. Herein, we describe the types of biosensors with the main focus on electrochemical biosensors fabricated for the detection of OPPs and carbamates pesticides. An overview of conventional techniques employed for pesticide detection is also discussed. This review aims to provide a glance of recently developed biosensors for some common pesticides like chlorpyrifos, malathion, parathion, paraoxon, and carbaryl which are present in food and environment samples.

Nitrogen-Doped Carbon Dots for Selective and Rapid Gene Detection of Human Papillomavirus Causing Cervical Cancer.

According to WHO, cervical cancer is considered as one of the most frequently diagnosed cancers and the fourth main source of cancer death in women in 2020 worldwide. Hence, there is a need for development of cervical cancer screening with new rapid and cost-effective methods. Although there are few methods available for HPV identification, these techniques are less sensitive, time-consuming, and costly. An ultra-sensitive, selective, and label-free DNA-based impedimetric electrochemical genosensor is developed in this study to detect HPV-18 for cervical cancer. Electrochemical analysis was performed for the characterization of the sensing platform and for the detection of analyte. A single-stranded 25mer oligonucleotide DNA probe was immobilized onto a nitrogen-doped carbon nanodot-modified ITO electrode. Furthermore, the hybridization event was measured by testing the complementary single stranded DNA sequence in the samples. The sensor could distinguish between complementary as well as non-complementary sequences. Herein, impedance quantification demonstrated a limit of detection of 0.405 fM. The developed genosensor showed high selectivity toward HPV-18 in the clinical samples. This sensing platform can be considered as a rapid and selective method for the screening of HPV-18.

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.

Nanohybrid-based immunosensor prepared for Helicobacter pylori BabA antigen detection through immobilized antibody assembly with @ Pdnano/rGO/PEDOT sensing platform.

The gastric colonization of human hosts by Helicobacter pylori (H. pylori) increases the risk of developing gastritis, ulcers and gastric cancer. To detect H. pylori, a nanohybrid-based BabA immunosensor is developed herein. BabA is an outer membrane protein and one of the major virulence factors of H. pylori. To design the immunosensor, an Au electrode is loaded with palladium nanoparticles (Pdnano) by electrodeposition to generate reduced graphene oxide (rGO)/poly(3,4-ethylenedioxythiophene) (PEDOT). The immobilization of these nanostructured materials imparts a large surface area and electroconductivity to bio-immune-sensing molecules (here, the BabA antigen and antibodies). After optimization, the fabricated immunosensor has the ability to detect antigens (H. pylori) in a linear range from 0.2 to 20 ng/mL with a low LOD (0.2 ng/mL). The developed immunosensor is highly specific, sensitive and reproducible. Additionally, in silico methods were employed to better understand the hybrid nanomaterials of the fabricated Pdnano/rGO/PEDOT/Au electrode. Simulations performed by molecular docking, and Metropolis Monte Carlo adsorption studies were conducted. The results revealed that the hybrid nanomaterials exhibit a stable antigen-antibody complex of BabA, yielding the lowest binding energy in relation to the electrode materials, emphasizing the functionality of the constructed electrodes in the electrochemical immunosensor.

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.

Synergistic effect of 2D material coated Pt nanoparticles with PEDOT polymer on electrode surface interface for a sensitive label free Helicobacter pylori CagA(Ag-Ab) immunosensing.

Helicobacter pylori (H. pylori) immunosensor based on platinum nanoparticles/poly(3,4-ethylenedioxythiophene)/reduced graphene oxide (Ptnano/PEDOT/red-GOx) modified gold electrode (Au-ET) was stepwise fabricated for the detection of cytotoxin-associated gene A antibody (CagA antibody). H. pylori is a microaerophillic and a Gram-negative bacteria that causes gastric ulcer leading eventually to adenocarcinoma (gastric cancer) in the later stage. H. pylori colonizes inner lining of human stomach. The developed diagnostic sensing interface would allow H. pylori (stomach infection) detection in early stage and would be a great contribution in clinical laboratories. In order to fabricate the immunosensor, CagA antigen was immobilized over the Ptnano/PEDOT/red-GOx modified Au-ET. Afterwards, the modified electrode was used for immuno-sensing of H. pylori specific Cag A antibodies in serum. At lower voltage the modified Ptnano/PEDOT/red-GOx/Au-ET shows an amplified sensing at the interface that makes the sensor more sensitive and specific. CagA is a virulence factor produced by H. pylori was determined by sudden decrease in the current. The laboratory synthesized nano composites were characterised by Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM) studies. The sensor had excellent linear range of 0.1 ng/ml to 30 ng/ml by limiting the detection range up to 0.1 ng/ml. Moreover, the novel immunosensor formed had good accuracy, precision and reliability. The immunosensor also showed an excellent storage stability by retaining 60-70% of its initial activity until 60 days kept at 4 °C. Highly sensitive interface of CagA antigen@Ptnano/PEDOT/red-GOx/Au-ET shows a promising future for H. pylori detection in diagnosis of stomach ulcer and stomach cancer.

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.

Helicobacter pylori targets mitochondrial import and components of mitochondrial DNA replication machinery through an alternative VacA-dependent and a VacA-independent mechanisms.

Targeting mitochondria is a powerful strategy for pathogens to subvert cell physiology and establish infection. Helicobacter pylori is a bacterial pathogen associated with gastric cancer development that is known to target mitochondria directly and exclusively through its pro-apoptotic and vacuolating cytotoxin VacA. By in vitro infection of gastric epithelial cells with wild-type and VacA-deficient H. pylori strains, treatment of cells with purified VacA proteins and infection of a mouse model, we show that H. pylori deregulates mitochondria by two novel mechanisms, both rather associated with host cell survival. First, early upon infection VacA induces transient increase of mitochondrial translocases and a dramatic accumulation of the mitochondrial DNA replication and maintenance factors POLG and TFAM. These events occur when VacA is not detected intracellularly, therefore do not require the direct interaction of the cytotoxin with the organelle, and are independent of the toxin vacuolating activity. In vivo, these alterations coincide with the evolution of gastric lesions towards severity. Second, H. pylori also induces VacA-independent alteration of mitochondrial replication and import components, suggesting the involvement of additional H. pylori activities in mitochondria-mediated effects. These data unveil two novel mitochondrial effectors in H. pylori-host interaction with links on gastric pathogenesis.

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.