Recent advances to overcome the burden of Japanese encephalitis: A zoonotic infection with problematic early detection.

Japanese encephalitis (JE) is a vector-borne neurotropic disease caused by Japanese encephalitis virus (JEV) associated with high mortality rate distributed from Eastern and Southern Asia to Northern Queensland (Australia). The challenges in early detection and lack of point-of-care biomarkers make it the most important Flavivirus causing encephalitis. There is no specific treatment for the disease, although vaccines are licenced. In this review, we focussed on point-of-care biomarkers as early detection tools and developing the effective therapeutic agents that could halt JE. We have also provided molecular details of JEV, disease progression, and its pathogenesis with recent findings which might bring insights to overcome the disease burden.

Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study.

BACKGROUND & AIMS: Clinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry. METHODS: Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 µg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. RESULTS: Overall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81-10.50; P < .01; OR, 3.02; 95% CI, 1.89-4.84; P < .01; and OR, 1.86; 95% CI, 1.15-2.99; P = .01; and OR, 3.27; 95% CI, 1.96-5.45; P < .01; OR, 1.87; 95% CI, 1.14-3.07; P = .01; and OR, 1.81; 95% CI, 1.06-3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events. CONCLUSIONS: Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes.

Value added bioactive compounds from fruits & vegetables waste for assessing their antimicrobial activity.

Since ancient time, plants and there parts have been used widely against dreadful pathogens due to ability of killing microbes. Waste from fruits and vegetables are pulling in more interest in exploration due to their therapeutic properties such as anti-pathogenic activity. In the present study antimicrobial and cytotoxicity properties of herbal combination prepared from peels of Allium cepa, Cucumis sativus, Citrus reticulata, and Mangifera indica were investigated. The herbal combination was tested for broad spectrum antimicrobial activity against Streptococcus mutans, Bacillus licheniformis, Lactobacillus plantarum, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii. The presence of phytochemical markers such as phenolics and flavanoids were also investigated. The results revealed that the herbal combination exhibited antimicrobial activity against S. mutans, B. licheniformis, L. plantarum, E. coli and moderate against P. aeruginosa and C. freundii. The presence of phenolics (798 ± 1.52 µg/g) and flavanoids (355.3 ± 2.081 µg/g) was also detected. Also, the herbal combination contains flavanoids such as quercetin and rutin was confirmed with the help of column chromatography, high-performance liquid chromatography (HPLC), fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) analysis. The herbal combination helps in the proliferation of L929 cells without affecting their viability was confirmed by MTT assay. The results of the present research suggests the possibility to use herbal combination as source for plausible antibacterial agent which could be isolated and used as a lead candidate for the development of antibacterial drug that help to limit or stop infectious illnesses caused by different pathogenic microbes.

Th1-Th2 and M1-M2 interplay sculpt Aeromonas hydrophila pathogenesis in zebrafish (Danio rerio).

Aeromonas hydrophila is an important aquatic zoonotic pathogen that causes septicemia, necrotizing fasciitis and gastroenteritis in various aquatic and non-aquatic animals. However, the pathogenesis of A. hydrophila is not fully understood. Here, we examined the pathogenicity and histopathology of A. hydrophila in the zebrafish (Danio rerio) model system. We found that the intensity of symptoms and mortality is dose-dependent. Bacterial colonization studies demonstrated that A. hydrophila never cleared out from the fish body but stayed in a state of inactivity till it enters a fresh host. Reinfection studies showed that exposure to A. hydrophila provides immunity against future infection and hence improves fish survival. Gene expression studies revealed the crosstalk between T-helper cell and macrophage responses in fish immune system in response to A. hydrophila and infection memory. Histopathological studies showed that symptoms of tissue damage and inflammation lasted for less duration with less intensity in immunized fish when compared to non-immunized fish. Together, our results suggest that the zebrafish model is a useful system in studying the interplay between A. hydrophila pathogenesis, persistence and immunity.

Preclinical assessment of stem of Nicotiana tabacum on excision wound model.

Agro-waste material derived from N. tabacum has shown enormous potential antioxidant and antimicrobial activity. Hence in the present study, we investigated the wound healing efficacy of ethanolic extract of stem of Nicotiana tabacum on wistar rat model. Ethanolic extract prepared from defatted stem was to check various phytochemicals using spectrophotometric and chromatographic technique. The antioxidant potential was determined by FRAP and Reducing Power assay in extract. Cytotoxicity of extracts was determined using mouse fibroblast L929 cell lines by MTT assay. In vivo angiogenic activity was observed on chick chorioallantoic membrane (CAM) model by observing blood vessels formation and its branching. In vivo wound healing activity was observed on excision wounds in rat model by quantifying percentage of wound contraction, antioxidant activity and histopathology studies. From the present study, polyphenols, tannins and alkaloids were found to be determined in the ethanolic extract by means of spectrophotometric and chromatographic analysis against standards. Antioxidant assay revealed maximum antioxidant potential in ethanolic extract. Cytotoxic effect of extract has not been shown on L929 cell line. From CAM model, extract has shown growth of blood vessels formation at concentration of 480 µg/ml. Topical application of extracts on excision wounds, revealed wound healing activity i.e. 98.7% ± 0.002 on 14th day as well as enzymatic activity (SOD, CAT, GST) and non enzyme content (GSH and Lipid peroxidation) has been found to be high in granulated tissue. Hisopathological studies confirmed the re-epithelization in skin wounds. It can be concluded that stem of N. tabacum can be used as herbal remedy in wound healing process as a topical application.

Cliv-92-Loaded Glycyrrhetinic Acid-Modified Chitosan Nanoparticles for Enhanced Hepatoprotection-Preparation, Characterization, and In Vivo Evaluation.

Cliv-92 is a mixture of three structurally similar coumarinolignoids and a proven hepatoprotective agent. Low aqueous solubility and poor bioavailability are notable hindrances for its further use. Therefore, glycyrrhetinic acid-linked chitosan nanoparticles loaded with Cliv-92 were prepared for active targeting to the liver. The nanoparticles were prepared by the ionic gelation method to avoid the use of toxic solvents/rigorous agitation. The method of preparation was optimized using a central composite design with independent variables, namely polymer: drug ratio (3:1, w/w), crosslinker concentration (0.5%), and stirring speed (750 rpm). The optimized nanoparticles had a mean particle size of 185.17 nm, a polydispersity index of 0.41, a zeta potential of 30.93 mV, and a drug loading of 16.30%. The prepared formulation showed sustained release of approximately 63% of loaded Cliv-92 over 72 h. The nanoparticles were freeze-dried for long-term storage and further characterized. The formulation was found to be biocompatible for parenteral delivery. In vivo imaging study showed that optimized nanoparticles were preferentially accumulated in the liver and successfully targeting the liver. The present study successfully demonstrated the improved pharmacokinetic properties (≈12% relative bioavailability) and efficacy profile (evidenced by in vivo and histopathological studies) of fabricated Cliv-92 nanoparticles.

Variations in the antioxidant and free radical scavenging under induced heavy metal stress expressed as proline content in chickpea.

This study pertains to the effects of heavy metal salts viz., copper (Cu), manganese (Mn), lead (Pb) and zinc (Zn) on the chickpea accession ICC-4812. The salts were given as treatments to the chickpea seeds at various ascending levels of doses till proving toxic. The treatment of 24 h soaked and swollen seeds were then extended to 7 days duration from the date of treatment. Atomic absorption spectrophotometric analysis of bioassay tissue Cicer, showed maximum uptake of 9.41 mg/g and minimum of 1.65 mg/g tissue dry weight for Pb and Zn respectively. The study reveals that enhanced antioxidant responses are associated with substantial proline accumulation indicating induced stress. Ferric reducing antioxidant power assay measuring antioxidant activity was highest in the chickpea seedling treated with Zn, whereas, free radical scavenging activity was highest in the treatments with Mn. The total phenolic and flavonoid contents ranged between 0.24-0.97 and 0.27-1.00 mg/g of dry matter content respectively. Higher Pb and Zn doses seem to elicit higher proline levels therefore, suggesting an extreme condition of induced abiotic stress. Dose dependent protein oxidation coupled with DNA degradation was observed in all treatments, depicting genotoxicity. Unweighted pair-group method arithmetic average analysis presented similarity coefficients between the treatments.

Biochemical diversity evaluation in chickpea accessions employing mini-core collection.

The seeds of chickpea provide an exceptional source of dietary proteins and is one of the important legumes in both developed and developing countries over the world. The available germplasm of cultivated chickpea is deficient in desired biochemical signatures. To identify new sources of variations for breeding, reduced subsets of germplasm such as mini-core collection can be explored as an effective resource. In the present investigation, mini-core collections consisting of 215 accessions of chickpea were extensively evaluated for tapping biochemical diversity. Analysis included ten biochemical parameters comprising total protein, total free amino acids, phytic acid, tannin, total phenolics, total flavonoids, lectin, DPPH radical scavenging activity, in vitro digestibility of protein and starch. The spectrum of diversity was documented for total protein (4.60-33.90%), total free amino acids (0.092-9.33 mg/g), phytic acid (0.009-4.06 mg/g), tannin (0.232-189.63 mg/g), total phenolics (0.15-0.81 mg/g), total flavonoids (0.04-1.57 mg/g), lectin (0.07-330.32 HU/mg), DPPH radical scavenging activity (26.74-49.11%), in vitro protein digestibility (59.45-76.22%) and in vitro starch digestibility (45.63-298.39 mg of maltose/g). The principal component analysis revealed association of chickpea higher protein content to the lower level of total phenolics and flavonoid contents. The dendrogram obtained by unweighted pair group method using arithmetic average cluster analysis grouped the chickpea accessions into two major clusters. This is the first comprehensive report on biochemical diversity analysed in the mini-core chickpea accessions. The ultimate purpose of conducting such studies was to deliver information on nutritional characteristics for effective breeding programmes. Depending on the objectives of the breeding aforesaid accessions could be employed as a parent.

Fluoride exposure abates pro-inflammatory response and induces in vivo apoptosis rendering zebrafish (Danio rerio) susceptible to bacterial infections.

The present study describes the immunotoxic effect of chronic fluoride exposure on adult zebrafish (Danio rerio). Zebrafish were exposed to fluoride (71.12 mg/L; 1/10 LC50) for 30 d and the expression of selected genes studied. We observed significant elevation in the detoxification pathway gene cyp1a suggesting chronic exposure to non-lethal concentration of fluoride is indeed toxic to fish. Fluoride mediated pro-oxidative stress is implicated with the downregulation in superoxide dismutase 1 and 2 (sod1/2) genes. Fluoride affected DNA repair machinery by abrogating the expression of the DNA repair gene rad51 and growth arrest and DNA damage inducible beta a gene gadd45ba. The upregulated expression of casp3a coupled with altered Bcl-2 associated X protein/B-cell lymphoma 2 ratio (baxa/bcl2a) clearly suggested chronic fluoride exposure induced the apoptotic cascade in zebrafish. Fluoride-exposed zebrafish when challenged with non-lethal dose of fish pathogen A. hydrophila revealed gross histopathology in spleen, bacterial persistence and significant mortality. We report that fluoride interferes with system-level output of pro-inflammatory cytokines tumour necrosis factor-α, interleukin-1ß and interferon-γ, as a consequence, bacteria replicate efficiently causing significant fish mortality. We conclude, chronic fluoride exposure impairs the redox balance, affects DNA repair machinery with pro-apoptotic implications and suppresses pro-inflammatory cytokines expression abrogating host immunity to bacterial infections.

Liver test abnormalities predict complicated disease behaviour in patients with newly diagnosed Crohn's disease.

BACKGROUNDS: In coeliac disease, the prevalence of liver test abnormalities (LTAs) is higher in patients with more severe mucosal inflammation. In Crohn's disease, prognosis is related to the severity of mucosal inflammation. AIM: The aim of this study was to investigate whether the presence of LTA predicts the occurrence of complicated disease behaviour in newly diagnosed Crohn's disease. METHODS: A retrospective cohort study was performed in patients newly diagnosed with Crohn's disease between 2002 and 2011. The complicated disease was defined as the occurrence of stricturing and/or perforating disease. LTAs were defined as a value of any of alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) over the upper limit of normal. RESULTS: Three hundred eighty-three patients were included, of whom 34.1% had LTA. LTAs were mostly mild (less than two times the upper limit of normal). During the 5-year follow-up, 33.1% of patients in the group with LTA developed complicated disease behaviour compared to 14.6% in patients without LTA (p < 0.001). The presence of LTA was identified as a risk factor for complicated disease behaviour (HR 2.6, 95% confidence interval (CI) 1.5-4.2, p < 0.0001). CONCLUSIONS: In newly diagnosed Crohn's disease, the presence of LTA was an independent risk factor for the development of complicated disease behaviour.

In vitro evaluation of excess copper affecting seedlings and their biochemical characteristics in Carthamus tinctorius L. (variety PBNS-12).

The present study was focused to recognize the changes in the Safflower (Carthamus tinctorius L. variety PBNS-12), when exposed to different concentration of copper (25, 50 and 100 µM) along with control (0.5 µM) for 10 and 20 days. This experiment used Hoagland's nutrient solution to meet the external nutrient conditions, which includes micro and macronutrients equivalent to soil solution with copper sulphate (CuSO4. 5H2O) as a metal stress. The plant samples were harvested after 10 and 20 days. The effect of increased concentrations of copper was indicated by the reduction in overall growth with reduced fresh and dry weight. Copper stress caused significant increase in the non- enzymatic antioxidants (polyphenols and flavonoids) in leaves of treated safflower seedlings as compared to the control. Also, enhanced accumulation of proline was observed in the safflower leaves. In response to excess copper concentration, the level of MDA content was found to be increased. The results showed that the copper has time and dose-dependent effects on safflower seedlings.

Host-mediated gene silencing of a single effector gene from the potato pathogen Phytophthora infestans imparts partial resistance to late blight disease.

RNA interference (RNAi) has proved a powerful genetic tool for silencing genes in plants. Host-induced gene silencing of pathogen genes has provided a gene knockout strategy for a wide range of biotechnological applications. The RXLR effector Avr3a gene is largely responsible for virulence of oomycete plant pathogen Phytophthora infestans. In this study, we attempted to silence the Avr3a gene of P. infestans through RNAi technology. The P. infestans inoculation resulted in lower disease progression and a reduction in pathogen load, as demonstrated by disease scoring and quantification of pathogen biomass in terms of Pi08 repetitive elements, respectively. Transgenic plants induced moderate silencing of Avr3a, and the presence and/or expression of small interfering RNAs, as determined through Northern hybridization, indicated siRNA targeted against Avr3a conferred moderate resistance to P. infestans. The single effector gene did not provide complete resistance against P. infestans. Although the Avr3a effector gene could confer moderate resistance, for complete resistance, the cumulative effect of effector genes in addition to Avr3a needs to be considered. In this study, we demonstrated that host-induced RNAi is an effective strategy for functional genomics in oomycetes.

Electric stimulations mediated beta lactam resistance reversal and correlation with growth dynamics of community acquired methicillin resistant Staphylococcus aureus.

The community associated methicillin resistant Staphylococcus aureus (CA-MRSA) is a serious issue of public health. Here, we conducted an experimental approach to determine: (i) the optimal significant stimulation range of electrical current for effective checking of CA-MRSA growth; (ii) the effect of electrical stimulations on methicillin susceptibility and possible beta lactam resistance reversal; and (iii) the variation in the level of ATP as function of exposure to electric current. An 8 chambered electrical system was developed for DC flow in control and test sets, with and without drug (oxacillin 4 mg/ml). Measurement of growth by CFU/ml and spectrometry, susceptibility and ATP levels were calculated and interpreted. Linear pattern in reduction of ATP was observed with respect to the intensity of electric current (EC) and an enhanced inhibitory effect was explicit with 1000 microampere (µA) with 30 min exposure. At 4000 µA exposure to DC at 180 min and in combination of drug (µA+D), the growth of CA-MRSA was substantially checked to 0.23 absorbance in comparison to current without drug and the effect of DC electrical current to the culture showed that 10 µA, 100 µA and 4000 µA current exposure in combination of oxacillin (µA+D), markedly reduced the CFU to an average of 256.4. ATP level was linearly reduced with exposure to EC.

Chemical composition and acetylcholinesterase inhibitory activity of Artemisia maderaspatana essential oil.

CONTEXT: To date, there are no reports to validate the Indian traditional and folklore claims of Artemisia maderaspatana L. (syn. Grangea maderaspatana L.) (Asteraceae) for the treatment of Alzheimer's disease. OBJECTIVE: The present study characterizes the volatile components (non-polar compounds) of A. maderaspatana and evaluates its acetylcholinesterase inhibition potential. MATERIALS AND METHODS: The essential oils (yield 0.06% v/w) were obtained from fresh aerial part of A. maderaspatana. The characterization of volatile components (non-polar compounds) was performed by GC-MS data and with those of reference compounds compiled in the spectral library of in-house database. The in vitro acetylcholinesterase (AChE) inhibition of the volatile organic constituents (VOC's) of A. maderaspatana aerial part was evaluated in varying concentration ranges (0.70-44.75 µg/mL) with Ellman's method. RESULTS: The major components were α-humulene (46.3%), ß-caryophyllene (9.3%), α-copaene (8.2%), ß-myrcene (4.3%), Z(E)-α-farnesene (3.7%), and calarene (3.5%). Chemical variability among other Artemisia spp. from different climatic regions of India and countries namely Iran and France was observed. The experimental results showed that diverse volatile organic constituents of A. maderaspatana have significant acetylcholinesterase inhibitory activity (an IC50 value of 31.33 ± 1.03 µg/mL). This is the first report on the inhibition of acetylcholinesterase properties of essential oil of A. maderaspatana obtained from fresh aerial part. CONCLUSIONS: The present results indicate that essential oil of A. maderaspatana isolated from the northern region of India could inhibit AChE moderately. Therefore, the possibility of novel AChE inhibitors might exist in VOCs of this plant.

Retraction Note to: Pathogen virulence of Phytophthora infestans: from gene to functional genomics.

[This retracts the article DOI: 10.1007/s12298-012-0157-z.].

The first evidence of cholinesterases in skin mucus of carps and its applicability as biomarker of organophosphate exposure.

The presence of cholinesterase (ChE) activity in skin mucus of three carps, Cirrhinus mrigala, Labeo rohita, and Catla catla and its applicability as biomarker of the organophosphorus insecticide exposure were investigated. Biochemical characterization, using specific substrates and inhibitors, indicated that measured esterase activity in skin mucus was mainly owing to ChEs. Significant difference in the proportion of acetylcholinesterase and butyrylcholinesterase activities was observed in skin mucus of three carps. Enzyme kinetic analysis, using the substrate acetylthiocholine iodide revealed significantly high Vmax value in C. catla compared to that in L. rohita and C. mrigala. In contrast, Vmax value using the substrate butyrylthiocholine iodide was significantly high in C. mrigala than in L. rohita and C. catla. In vitro treatment of skin mucus of three carps, with the organophosphorus insecticide Nuvan®, showed strong inhibition of ChE activities. In vivo experiments conducted using C. mrigala and exposing the fish to the sublethal test concentrations (5 and 15 mg/L) of the insecticide also revealed significant inhibition of ChE activity in mucus. In C. mrigala, exposed to the sublethal test concentrations of the insecticide for 4 days and then kept for recovery for 16 days, mucus ChE activity recovered to the control level. Thus, ChE activity in skin mucus could be considered a good biomarker of the organophosphorus insecticide exposure to fish and a useful tool in monitoring environmental toxicity.

Potential involvement of ferroptosis in BPA-induced neurotoxicity: An in vitro study.

BACKGROUND: Ferroptosis is a newly recognized cell death pathway having distinct characteristics compared to traditional cell death pathways such as apoptosis, necroptosis, or autophagy. However, the potential involvement of ferroptosis in bisphenol A (BPA)-induced neurotoxicity has not been well explored so far. In present study, we analyzed the relationship between ferroptosis and BPA-induced neurotoxicity. METHODS: In this study, a human neuroblastoma cell line, SH-SY5Y, was treated with BPA, ferrostatin-1 (FS-1, ferroptosis inhibitor) and RSL-3 (ferroptosis inducer). The cell viability was measured using MTT assay. Additionally, the levels of lipid peroxidation, total iron content, reactive oxygen species (ROS) generation, and nitrite content were measured to evaluate the key markers of ferroptosis. To further confirm the involvement of ferroptosis in BPA-induced neurotoxicity, other ferroptosis markers such as glutathione peroxidase (GPx) activity, total glutathione contents and antioxidant parameters were also evaluated. RESULTS: The cell viability of SH-SY5Y cells was down-regulated by BPA treatment in a concentration-dependent manner, the cell viability at 0.1 µM concentration was 97.63% whereas at highest BPA concentration i.e. 10 µM, the cell viability was 86.05% (p < 0.0001). Also the antioxidant parameters including catalase and superoxide dismutase activity of neuronal cells were down-regulated upon BPA exposure. However, the levels of lipid peroxidation, total iron, reactive oxygen species, and nitrite contents were increased in a concentration-dependent manner which could be rescued by FS-1 and exacerbated by RSL-3. The total iron in SH-SY5Y cells at 0.1 µM concentration was found to be 1.2 fold (p < 0.05) of control and at highest BPA concentration total iron was about 1.41 fold (p < 0.001) of control. CONCLUSIONS: The present study indicated that, ferroptosis plays an important role in the progression of BPA-induced neurotoxicity, and ferroptosis may become a novel target in the treatment of various neurological disorders.

Prostate-Specific Membrane Antigen-Targeted NIR Phototheranostics for Prostate Cancer.

The evolution of targeted cancer theranostics has revolutionized personalized medicine by integrating diagnostic and therapeutic capabilities. Prostate-specific membrane antigen (PSMA) has emerged as a key theranostic target in the context of prostate cancer, paving the way for the clinical approval of multiple drugs. However, the persistent challenge of off-target toxicity, which plagues both conventional and advanced treatment modalities such as targeted chemotherapy and radiotherapy, thus demands further innovation. Considering this critical issue, this review discusses the recent advances in the binary treatment techniques, i.e., phototherapies, that have the potential to circumvent the key concern of off-target toxicity associated with personalized chemotherapy and radiotherapy. Precisely, an up-to-date overview of the latest developments in the near-infrared (NIR)-based phototheranostic strategies for prostate cancer by targeting PSMA has been presented. Furthermore, we have discussed the associated particulars that require specific attention in enhancing the translational potential of phototheranostic techniques.

Enhancing clinical drug trial monitoring with blockchain technology.

BACKGROUND: Clinical drug trials are intricate, involving numerous stakeholders, substantial data, and stringent regulations. Traditional systems for recording, storing, and sharing trial data often face data integrity, transparency, security, and interoperability challenges. The utilization of blockchain technology has emerged as a transformative influence in various industries, and its potential within healthcare, particularly in clinical drug trials, is increasingly gaining recognition. METHODS: Blockchain technology presents a decentralized and immutable ledger system that holds promise in effectively addressing these challenges. As the healthcare industry continues its journey of digital transformation, the incorporation of blockchain technology for monitoring clinical drug trials represents a paradigm shift that can result in more reliable, efficient, and transparent trials. RESULTS AND CONCLUSION: This review explores the innovative application of blockchain technology in transforming the monitoring and management of clinical drug trials and provides a comprehensive overview of the possibilities, challenges, and future directions of blockchain-based monitoring in the context of clinical drug trials, contributing to the progress of both blockchain technology and healthcare research practices.

Exploring the potential of two Pseudomonas species to produce vincristine from vinblastine via biotransformation.

A biotransformation pair consisting of vinblastine: vincristine present in the Catharanthus roseus plant is of immense pharmacological significance. In this study, we successfully transformed vinblastine into vincristine outside the plant using Pseudomonas aeruginosa 8485 and Pseudomonas fluorescens 2421 and evaluated the antiangiogenic potential of thus produced vincristine through the CAM assay. The toxicity assay showed that both Pseudomonas spp. can tolerate varying concentrations (25-100 µl of 1 mg/ml) of vinblastine. The biotransformation was performed in a liquid nutrient broth medium containing vinblastine (25-100 µl), and Pseudomonas spp. inoculums (50-150 µl) by incubating at 30 °C and 37 °C, respectively for 8 days. The process was optimized for substrate and culture concentrations, pH, temperature, and rotation speed (rpm) for the highest conversion. Analysis using LC-MS/MS confirmed the presence of vincristine as a product of the vinblastine biotransformation by two Pseudomonas spp. P. fluorescens 2421 showed a faster conversion rate with 95% of vinblastine transformed within 24 h than P. aeruginosa 8485, which demonstrated a conversion rate of 92% on the 8th day. From LC-MS/MS analysis, the optimal conditions for the reaction were determined as vinblastine (25 µl), microbial inoculums (150 µl or 200 × 106 and 210 × 106 CFU/ml), pH 7.4, rotation speed of 180 rpm, and temperatures of 30 °C and 37 °C with incubation time of 8 days. The vincristine produced exhibited potent antiangiogenic activity in the CAM assay reducing the thickness and branching of blood vessels in a dose-dependent manner. The study concludes that both Pseudomonas spp. showed promise for vincristine production from vinblastine, without compromising its antiangiogenic properties.