The Emerging Role of Natural Products in Cancer Treatment.

The exploration of natural products as potential agents for cancer treatment has garnered significant attention in recent years. In this comprehensive review, we delve into the diverse array of natural compounds, including alkaloids, carbohydrates, flavonoids, lignans, polyketides, saponins, tannins, and terpenoids, highlighting their emerging roles in cancer therapy. These compounds, derived from various botanical sources, exhibit a wide range of mechanisms of action, targeting critical pathways involved in cancer progression such as cell proliferation, apoptosis, angiogenesis, and metastasis. Through a meticulous examination of preclinical and clinical studies, we provide insights into the therapeutic potential of these natural products across different cancer types. Furthermore, we discuss the advantages and challenges associated with their use in cancer treatment, emphasizing the need for further research to optimize their efficacy, pharmacokinetics, and delivery methods. Overall, this review underscores the importance of natural products in advancing cancer therapeutics and paves the way for future investigations into their clinical applications.

An insight into the role of protein kinases as virulent factors, regulating pathogenic attributes in Candida albicans.

Candida albicans is a polymorphic, opportunistic pathogen, member of normal human microbiome causing candidiasis. It causes wide range of infections from superficial skin infections to life-threatening systemic infections. The pathogenicity in C. albicans attributes through several morphological characteristics and virulence factors. These morphological features are regulated by various molecules among which kinases are the most important. Several kinases and kinase signaling cascades play a well established role in Candidiasis. In this review we present an update on our current understanding of the pathogenicity attributes which is regulated by kinases as virulence factors.

Identification of phytocompounds from Houttuynia cordata Thunb. as potential inhibitors for SARS-CoV-2 replication proteins through GC-MS/LC-MS characterization, molecular docking and molecular dynamics simulation.

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive viral disease outbreak of international concerns. The present study is mainly intended to identify the bioactive phytocompounds from traditional antiviral herb Houttuynia cordata Thunb. as potential inhibitors for three main replication proteins of SARS-CoV-2, namely Main protease (Mpro), Papain-Like protease (PLpro) and ADP ribose phosphatase (ADRP) which control the replication process. A total of 177 phytocompounds were characterized from H. cordata using GC-MS/LC-MS and they were docked against three SARS-CoV-2 proteins (receptors), namely Mpro, PLpro and ADRP using Epic, LigPrep and Glide module of Schrödinger suite 2020-3. During docking studies, phytocompounds (ligand) 6-Hydroxyondansetron (A104) have demonstrated strong binding affinity toward receptors Mpro (PDB ID 6LU7) and PLpro (PDB ID 7JRN) with G-score of - 7.274 and - 5.672, respectively, while Quercitrin (A166) also showed strong binding affinity toward ADRP (PDB ID 6W02) with G-score -6.788. Molecular Dynamics Simulation (MDS) performed using Desmond module of Schrödinger suite 2020-3 has demonstrated better stability in the ligand-receptor complexes A104-6LU7 and A166-6W02 within 100 ns than the A104-7JRN complex. The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP. Present findings confer opportunities for 6-Hydroxyondansetron and Quercitrin to be developed as new therapeutic drug against COVID-19.

Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK-HER2 and VEGFR2 receptors, by in silico approach.

Breast and stomach cancer is reported as a leading cause for human mortality across the world. The overexpression of receptor tyrosine kinase (RTK) proteins, namely the human epidermal growth factor receptor2 (HER2) and the vascular endothelial growth factor receptor2 (VEGFR2), is reported to be responsible for development and metastasis of breast and stomach cancer. Although several synthetic tyrosine kinase inhibitors (TKIs) as drug candidates targeting RTK-HER2 and VEGFR2 are currently available in the market, these are expensive with the reported side effects. This confers an opportunity for development of alternative novel tyrosine kinase inhibitors (TKIs) for RTK-HER2 and VEGFR2 receptors from the botanical sources. In the present study, we characterized 47 bioactive phytocompounds from the methanol extracts of the rhizomes of Asiatic traditional medicinal herbs-Panax bipinnatifidus and Panax pseudoginseng, of Indian Himalayan landraces using HPLC, GC-MS and high-sensitivity LC-MS tools. We performed molecular docking and molecular dynamics simulation analysis using Schrödinger suite 2020-3 to confirm the TKI phytocompounds showing the best binding affinity towards RTK-HER2 and VEGFR2 receptors. The results of molecular docking studies confirmed that the phytocompound (ligand) luteolin 7-O-glucoside (IHP15) showed the highest binding affinity towards receptor HER2 (PDB ID: 3PP0) with docking score and Glide g score (G-Score) of - 13.272, while chlorogenic acid (IHP12) showed the highest binding affinity towards receptor VEGFR2 (PDB ID: 4AGC) with docking score and Glide g score (G-Score) of - 10.673. Molecular dynamics (MD) simulation analysis carried out for 100 ns has confirmed strong binding interaction between the ligand and receptor complex [luteolin 7-O-glucoside (IHP15) and HER2 (PDB ID: 3PP0)] and is found to be stabilized within 40 to 100 ns of MD simulation, whereas ligand-receptor complex [chlorogenic acid (IPH12) and VEGFR2 (PDB ID: 4AGC)] also showed strong binding interaction and is found to be stabilized within 18-30 ns but slightly deviated during 100 ns of MD simulation. In silico ADME-Tox study using SwissADME revealed that the ligands luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) have passed majority parameters of the common drug discovery rules. The present study has confirmed luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) as potential tyrosine kinase inhibitors (TKIs) which were found to inhibit RTKs-HER2 and VEGFR2 receptor proteins, and thus paving the way for development of alternative potential TKIs (drug molecules) for treatment of HER2- and VEGFR2-positive breast and stomach cancer.

Development of potent and selective Cathepsin C inhibitors free of aortic binding liability by application of a conformational restriction strategy.

Cathepsin C plays a key role in the activation of several degradative enzymes linked to tissue destruction in chronic inflammatory and autoimmune diseases. Therefore, Cathepsin C inhibitors could potentially be effective therapeutics for the treatment of diseases such as chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome (ARDS). In our efforts towards the development of a novel series of Cathepsin C inhibitors, we started working around AZD5248 (1), an α-amino acid based scaffold having potential liability of aortic binding. A novel series of amidoacetonitrile based Cathepsin C inhibitors were developed by the application of a conformational restriction strategy on 1. In particular, this work led to the development of a potent and selective Cathepsin C inhibitor 3p, free of aortic binding liability.

All-in-One: Sensing, Adsorptive Removal, and Photocatalytic Degradation of Nitro-Explosive Contaminants by Microporous Polycarbazole Polymer.

A highly multitasking 3D polycarbazole based microporous organic polymer (ACzMOP) is rationally prepared via a low-cost FeCl3 catalyzed polymerization route utilizing a newly developed Td -symmetric adamantane core tetracarbazolic monomer. The nitrogen-rich ACzMOP integrated with photo-redox active electron-rich π-conjugated polycarbazole modules featuring large BET surface area of 1568 m 2  g -1 , pore volume of 1.58 cc g -1 , excellent physicochemical stability, and strong fluorescence in both aqueous and solid phases. Aqueous suspension including ACzMOP coated paper strip is highly responsive to the aqueous solution of nitroaromatics especially 2,4-dinitrotoluene, an unavoidable intermediate of 2,4,6-trinitrotoluene contamination, with ultra-trace level detection capability (up to 0.32 ppb). The thin layer of solid polymer is capable of detecting nitroaromatic vapors, especially nitrotoluenes in a very sensitive manner. Moreover, the polymer exhibit record uptake of nitrotoluenes and nitrophenols with maximum uptake capability up to 510 mg g -1  setting a new benchmark among known porous materials. The polymer efficiently degrades toxic 4-nitrophenol to the value-added 4-aminophenol precursor (TOF = 0.143 h -1 ) via photocatalytic pathway. For the very first time, ACzMOP as a single material system is capable of efficiently sensing and removing all sorts of nitroaromatic contaminations with regenerability under mild washing/vacuum conditions.

Environment-Sensitive Fluorescence of 7-Nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-Labeled Ligands for Serotonin Receptors.

Serotonin is a neurotransmitter that plays a crucial role in the regulation of several behavioral and cognitive functions by binding to a number of different serotonin receptors present on the cell surface. We report here the synthesis and characterization of several novel fluorescent analogs of serotonin in which the fluorescent NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) group is covalently attached to serotonin. The fluorescent ligands compete with the serotonin1A receptor specific radiolabeled agonist for binding to the receptor. Interestingly, these fluorescent ligands display a high environmental sensitivity of their fluorescence. Importantly, the human serotonin1A receptor stably expressed in CHO-K1 cells could be specifically labeled with one of the fluorescent ligands with minimal nonspecific labeling. Interestingly, we show by spectral imaging that the NBD-labeled ligand exhibits a red edge excitation shift (REES) of 29 nm when bound to the receptor, implying that it is localized in a restricted microenvironment. Taken together, our results show that NBD-labeled serotonin analogs offer an attractive fluorescent approach for elucidating the molecular environment of the serotonin binding site in serotonin receptors. In view of the multiple roles played by the serotonergic systems in the central and peripheral nervous systems, these fluorescent ligands would be useful in future studies involving serotonin receptors.

Connecting Femtosecond Transient Absorption Microscopy with Spatially Coregistered Time Averaged Optical Imaging Modalities.

Multimodal all-optical imaging involving coregistered femtosecond transient absorption microscopy (TAM), time-integrated photoluminescence (PL), and steady-state modalities such as confocal reflectance and transmission offers an appealing approach to gain a comprehensive understanding of complex electronic excited-state phenomena in spatially heterogeneous systems. A unique combination of these modalities allows us to unravel not only the competing electronic excited-state dynamical processes but also the underlying morphological information with simultaneous high temporal and spatial resolution. However, correlating the various images obtained from time-resolved and time-independent modalities is generally nontrivial and particularly challenging when the electronic dynamics under study evolve in both time and space. Here, we demonstrate a new approach for rationally correlating time-resolved microscopy with coregistered time-integrated or steady-state modalities. Specifically, our approach involves an extended global lifetime analysis of the time-resolved microscopic data set to separate distinct dynamical processes taking place on commensurate time scales, and the resulting decay-associated amplitude maps (DAAMs) were applied to explore correlations with the images acquired using time-independent modalities. The feasibility of our approach was validated through analyzing a multimodal data set acquired from a thin film of chloride-containing mixed lead halide perovskites (CH3NH3PbI3-xClx) using femtosecond transient absorption, time-integrated PL, and confocal reflectance microscopies. Analysis of the results obtained enable us to gain new insight into the complex ultrafast relaxation dynamics in this highly heterogeneous system.

Cu2I2Se6: A Metal-Inorganic Framework Wide-Bandgap Semiconductor for Photon Detection at Room Temperature.

Cu2I2Se6 is a new wide-bandgap semiconductor with high stability and great potential toward hard radiation and photon detection. Cu2I2Se6 crystallizes in the rhombohedral R3̅m space group with a density of d = 5.287 g·cm-3 and a wide bandgap Eg of 1.95 eV. First-principles electronic band structure calculations at the density functional theory level indicate an indirect bandgap and a low electron effective mass me* of 0.32. The congruently melting compound was grown in centimeter-size Cu2I2Se6 single crystals using a vertical Bridgman method. A high electric resistivity of ∼1012 Ω·cm is readily achieved, and detectors made of Cu2I2Se6 single crystals demonstrate high photosensitivity to Ag Kα X-rays (22.4 keV) and show spectroscopic performance with energy resolutions under 241Am α-particles (5.5 MeV) radiation. The electron mobility is measured by a time-of-flight technique to be ∼46 cm2·V-1·s-1. This value is comparable to that of one of the leading γ-ray detector materials, TlBr, and is a factor of 30 higher than mobility values obtained for amorphous Se for X-ray detection.

Defect Antiperovskite Compounds Hg3Q2I2 (Q = S, Se, and Te) for Room-Temperature Hard Radiation Detection.

The high Z chalcohalides Hg3Q2I2 (Q = S, Se, and Te) can be regarded as of antiperovskite structure with ordered vacancies and are demonstrated to be very promising candidates for X- and γ-ray semiconductor detectors. Depending on Q, the ordering of the Hg vacancies in these defect antiperovskites varies and yields a rich family of distinct crystal structures ranging from zero-dimensional to three-dimensional, with a dramatic effect on the properties of each compound. All three Hg3Q2I2 compounds show very suitable optical, electrical, and good mechanical properties required for radiation detection at room temperature. These compounds possess a high density (>7 g/cm3) and wide bandgaps (>1.9 eV), showing great stopping power for hard radiation and high intrinsic electrical resistivity, over 1011 Ω cm. Large single crystals are grown using the vapor transport method, and each material shows excellent photo sensitivity under energetic photons. Detectors made from thin Hg3Q2I2 crystals show reasonable response under a series of radiation sources, including 241Am and 57Co radiation. The dimensionality of Hg-Q motifs (in terms of ordering patterns of Hg vacancies) has a strong influence on the conduction band structure, which gives the quasi one-dimensional Hg3Se2I2 a more prominently dispersive conduction band structure and leads to a low electron effective mass (0.20 m0). For Hg3Se2I2 detectors, spectroscopic resolution is achieved for both 241Am α particles (5.49 MeV) and 241Am γ-rays (59.5 keV), with full widths at half-maximum (FWHM, in percentage) of 19% and 50%, respectively. The carrier mobility-lifetime µτ product for Hg3Q2I2 detectors is achieved as 10-5-10-6 cm2/V. The electron mobility for Hg3Se2I2 is estimated as 104 ± 12 cm2/(V·s). On the basis of these results, Hg3Se2I2 is the most promising for room-temperature radiation detection.

A perspective on the recent progress in solution-processed methods for highly efficient perovskite solar cells.

Perovskite solar cells (PSCs) were developed in 2009 and have led to a number of significant improvements in clean energy technology. The power conversion efficiency (PCE) of PSCs has increased exponentially and currently stands at 22%. PSCs are transforming photovoltaic (PV) technology, outpacing many established PV technologies through their versatility and roll-to-roll manufacturing compatibility. The viability of low-temperature and solution-processed manufacturing has further improved their viability. This article provides a brief overview of the stoichiometry of perovskite materials, the engineering behind various modes of manufacturing by solution processing methods, and recommendations for future research to achieve large-scale manufacturing of high efficiency PSCs.

Perovskite Solar Cells with Near 100% Internal Quantum Efficiency Based on Large Single Crystalline Grains and Vertical Bulk Heterojunctions.

Imperfections in organometal halide perovskite films such as grain boundaries (GBs), defects, and traps detrimentally cause significant nonradiative recombination energy loss and decreased power conversion efficiency (PCE) in solar cells. Here, a simple layer-by-layer fabrication process based on air exposure followed by thermal annealing is reported to grow perovskite films with large, single-crystal grains and vertically oriented GBs. The hole-transport medium Spiro-OMeTAD is then infiltrated into the GBs to form vertically aligned bulk heterojunctions. Due to the space-charge regions in the vicinity of GBs, the nonradiative recombination in GBs is significantly suppressed. The GBs become active carrier collection channels. Thus, the internal quantum efficiencies of the devices approach 100% in the visible spectrum range. The optimized cells yield an average PCE of 16.3 ± 0.9%, comparable to the best solution-processed perovskite devices, establishing them as important alternatives to growing ideal single crystal thin films in the pursuit toward theoretical maximum PCE with industrially realistic processing techniques.

Tailoring the properties of surface-immobilized azobenzenes by monolayer dilution and surface curvature.

Photoswitching in densely packed azobenzene self-assembled monolayers (SAMs) is strongly affected by steric constraints and excitonic coupling between neighboring chromophores. Therefore, control of the chromophore density is essential for enhancing and manipulating the photoisomerization yield. We systematically compare two methods to achieve this goal: First, we assemble monocomponent azobenzene-alkanethiolate SAMs on gold nanoparticles of varying size. Second, we form mixed SAMs of azobenzene-alkanethiolates and "dummy" alkanethiolates on planar substrates. Both methods lead to a gradual decrease of the chromophore density and enable efficient photoswitching with low-power light sources. X-ray spectroscopy reveals that coadsorption from solution yields mixtures with tunable composition. The orientation of the chromophores with respect to the surface normal changes from a tilted to an upright position with increasing azobenzene density. For both systems, optical spectroscopy reveals a pronounced excitonic shift that increases with the chromophore density. In spite of exciting the optical transition of the monomer, the main spectral change in mixed SAMs occurs in the excitonic band. In addition, the photoisomerization yield decreases only slightly by increasing the azobenzene-alkanethiolate density, and we observed photoswitching even with minor dilutions. Unlike in solution, azobenzene in the planar SAM can be switched back almost completely by optical excitation from the cis to the original trans state within a short time scale. These observations indicate cooperativity in the photoswitching process of mixed SAMs.

Controllable Growth of Perovskite Films by Room-Temperature Air Exposure for Efficient Planar Heterojunction Photovoltaic Cells.

A two-step solution processing approach has been established to grow void-free perovskite films for low-cost high-performance planar heterojunction photovoltaic devices. A high-temperature thermal annealing treatment was applied to drive the diffusion of CH3NH3I precursor molecules into a compact PbI2 layer to form perovskite films. However, thermal annealing for extended periods led to degraded device performance owing to the defects generated by decomposition of perovskite into PbI2. A controllable layer-by-layer spin-coating method was used to grow "bilayer" CH3NH3I/PbI2 films, and then drive the interdiffusion between PbI2 and CH3NH3I layers by a simple air exposure at room temperature for making well-oriented, highly crystalline perovskite films without thermal annealing. This high degree of crystallinity resulted in a carrier diffusion length of ca. 800 nm and a high device efficiency of 15.6%, which is comparable to values reported for thermally annealed perovskite films.

Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part I.

We report analogue-based rational design and synthesis of two novel series of polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles, tethered to a biaryl system by a methyl-, ethyl- or propyl ether as PDE10A inhibitors. A number of analogues were prepared with variable chain length and evaluated for their ability to block PDE10A enzyme using a radiometric assay. Detailed SAR analyses revealed that compounds with an ethyl ether linker are superior in potency compared to compounds with methyl or propyl ether linkers. These compounds, in general, showed poor metabolic stability in rat and human liver microsomes. The metabolic profile of one of the potent compounds was studied in detail to identify metabolic liabilities of these compounds. Structural modifications were carried out that resulted in improved metabolic stability without significant loss of potency.

Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: part II.

We report the design and synthesis of novel pyrrolo[3,2-b]quinoline containing heteroarene ethers as PDE10A inhibitors with good to excellent potency, selectivity and metabolic stability. Further optimization of this primary series resulted in the identification of 1-methyl-3-(4-{[3-(pyridine-4-yl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrolo[3,2-b]pyridine 13a with good hPDE10A potency (IC50: 6.3 nM), excellent selectivity over other related PDEs and desirable physicochemical properties. The compound exhibited high peripheral and adequate brain levels upon oral dosing in rodents. The compound also showed excellent efficacy in multiple preclinical animal models related to psychiatric disorders, particularly schizophrenia.

The Simultaneous Application of Transcranial Magnetic Stimulation and Virtual Reality to Treat Cognitive Deficits Among Stroke Patients: A Randomized Controlled Trial.

Background and objective Integrating virtual reality (VR) and transcranial magnetic stimulation (TMS) offers a promising strategy for stroke rehabilitation, as it specifically focuses on reorganizing neural connections and activating brain activity in the cortex. The main goal is to create equitable connections between the brain's two hemispheres to enhance the execution of voluntary movements by stimulating the central executive network (CEN) to strengthen both motor and cognitive abilities. This study aims to propose a therapeutic approach that can improve cognitive recovery and overall quality of life in patients after a stroke. Methods A total of 69 participants were enrolled in the study based on certain inclusion and exclusion criteria. The patients underwent pre-assessment and were randomly allocated into three groups: Group 1 received simultaneous repetitive TMS (rTMS) and virtual reality treatment (VRT), Group 2 received rTMS combined with sham VRT, and Group 3 received sham stimulation with VRT, in a 1:1:1 ratio using opaque, sealed, and stapled envelopes (SNOSE). Post-assessment was carried out using the same measures: the National Institutes of Health Stroke Scale (NIHSS), Addenbrooke's Cognitive Test (ACE III), and Montreal Cognitive Assessment (MOCA). Statistical analysis was conducted to determine the specific outcomes. Data analysis was carried out using IBM SPSS Statistics version 29 (IBM Corp., Armonk, NY), employing student's t-test for within-group comparisons and repeated measures ANOVA for between-group comparisons. The significance level was set at 5%. Results The results demonstrated statistical significance in NIHSS scores across all treatment groups (p<0.001). Regarding cognitive outcomes, improvements were observed in memory, language, and overall cognitive performance (ACE III) within all groups (p<0.05), with significant between-group outcomes (p = 0.009, p = 0.01, p = 0.004, respectively), suggesting variations in treatment effects across cognitive domains. However, no significant differences between groups were found in terms of fluency and visuospatial skills (p = 0.49, p = 0.13), indicating no treatment effects in these domains. Conclusions Based on our findings, the combined intervention involving rTMS and VRT, compared to sham treatments, demonstrates promising outcomes in alleviating stroke severity and improving specific cognitive functions such as memory, language, and overall cognitive performance. Additionally, the combined administration offers a more effective therapy than when they are administered separately.

Enhanced anticancer activity of (-)-epigallocatechin-3-gallate (EGCG) encapsulated NPs toward colon cancer cell lines.

(-)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol of green tea, has chemo-preventive effects against various cancer cells. Nanoparticles (NPs) carrying different ligands are able to specifically interact with their receptors on different cancer cells that can provide effective release of cytotoxic drugs. In the present study, we have prepared EGCG entrapped NPs using PLGA (poly(d,l-lactide-co-glycolide)). Polyethylene glycol (PEG) and folic acid (FA) via double emulsion solvent evaporation (DESE) method obtained PLGA-EGCG (P-E), PLGA-PEG-EGCG (PP-E), and PLGA-PEG-FA-EGCG (PPF-E). Nanoformulations had been characterized with 1H NMR and FT-IR techniques, AFM, and DLS. PPF-E NPs showed an average size of 220 nm. Analysis of zeta potential confirmed the stability of NPs. HCT-116, HT-29, HCT-15, and HEK 293 cells were treated with both the prepared NPs and free EGCG (0-140 µM). Result showed PPF-E NPs had improved delivery, uptake and cell cytotoxicity toward human folic acid receptor-positive (FR+) colorectal cancer (CRC) cells as mainly on HCT-116 compared to HT-29, but not on the folic acid-negative cells (FR-) as HCT-15. PPF-E NPs enhanced intracellular reactive oxygen species (ROS) level in absence of N-acetyl-l-cysteine (NAC), elevated DNA fragmentation level, and increased apoptotic cell death at higher doses compared to other two NPs and free EGCG. In conclusion, PPF-E NPs exerted greater efficacy than PP-E, P-E, and free EGCG in HCT-116 cells.

Molecular mechanism of nanomaterials induced liver injury: A review.

The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.

Establishment of an intragastric surgical model using C57BL/6 mice to study the vaccine efficacy of OMV-based immunogens against Helicobacter pylori.

Chronic gastritis is one of the major symptoms of gastro-duodenal disorders typically induced by Helicobacter pylori (H. pylori). To date, no suitable model is available to study pathophysiology and therapeutic measures accurately. Here, we have presented a successful surgical infection model of H. pylori-induced gastritis in C57BL/6 mice that resembles features similar to human infection. The proposed model does not require any preparatory treatment other than surgical intervention. C57BL/6 mice were injected with wild-type SS1 (Sydney strain 1, reference strain) directly into the stomach. Seven days post infection, infected animals showed alterations in cytokine responses along with inflammatory cell infiltration in the lamina propria, depicting a prominent inflammatory response due to infection. To understand the immunogenicity and protective efficacy, the mice were immunized with outer membrane vesicles (OMVs) isolated from an indigenous strain with putative virulence factors of H. pylori [A61C (1), cag+/vacA s1m1]. In contrast to the non-immunized cohort, the OMV-immunized cohort showed a gradual increase in serum immunoglobulin(s) levels on the 35th day after the first immunization. This conferred protective immunity against subsequent challenge with the reference strain (SS1). Direct inoculation of H. pylori into the stomach influenced infection in a short time and, more importantly, in a dose-dependent manner, indicating the usefulness of the developed model for pathophysiology, therapeutic and prophylactic studies.