New ring-A modified cycloartane triterpenoids from Dysoxylum malabaricum bark: Isolation, structure elucidation and their cytotoxicity.

The Genus Dysoxylum (Meliaceae) consists of approximately 80 species that are abundant in structurally diverse triterpenoids. The present study focused on isolating new triterpenoids from the bark of Dysoxylum malabaricum, one of the predominant species of Dysoxylum present in India. The methanol-dichloromethane bark extract was subjected to LCMS profiling followed by silica gel column chromatography and HPLC analysis to target new compounds. Two new ring A-modified cycloartane-type triterpenoids (1 and 2) were isolated from the bark extract. Spectroscopic methods like NMR, HRESIMS data, and electronic circular dichroism calculations elucidated the structuresandabsolute configurations of the isolated compounds. These compounds were evaluated for their cytotoxic potential against breast cancer cells and displayed notable cytotoxicity. Compound 1 exhibited the highest cytotoxicity against the MDA-MB-231 cells and induced apoptotic cell death. Also, it was able to inhibit glucose uptake and increase nitric oxide production in breast cancer cells.

Unveiling the cytotoxic and anti-proliferative potential of green-synthesized silver nanoparticles mediated by Colletotrichum gloeosporioides.

Fungal endophytes are a putative source of bioactive metabolites that have found significant applications in nanomedicine due to their metabolic versatility. In the present study, an aqueous extract of the fungal endophyte, Colletotrichum gloeosporioides associated with a medicinal plant Oroxylum indicum, has been used for the fabrication of green silver nanoparticles (CgAgNPs) and further evaluated their cytotoxic and anti-proliferative activity. Bioanalytical techniques including UV-Vis spectral analysis revealed a sharp band at 435 nm and functional molecules from the aqueous extract involved in the synthesis of CgAgNPs were evidenced through FTIR. Further, the crystalline nature of CgAgNPs was determined through XRD analysis and microscopy techniques including AFM, TEM and FESEM demonstrated the spherical shape of CgAgNPs exhibiting a crystalline hexagonal lattice and the size was found to be in the range of 9-29 nm. The significant cytotoxic potential of CgAgNPs was observed against breast cancer cells, MDA-MB-231 and MCF-7 with IC50 values of 18.398 ± 0.376 and 38.587 ± 1.828 µg mL-1, respectively. The biochemical study revealed that the treatment of MDA-MB-231 and MCF-7 cells with CgAgNPs reduces glucose uptake, suppresses cell proliferation, and enhances LDH release, indicating reduced cell viability and progression. Moreover, our research revealed differential expression of genes associated with apoptosis, cell cycle inhibition and metastasis suppression, evidencing anti-proliferative activity of CgAgNPs. The main objective of the present study is to harness anti-breast cancer activity of novel biogenic nanoparticles synthesized using the aqueous extract of O. indicum associated C. gloeosporioides and study the underlying mechanistic pathway exerted by these mycogenic nanoparticles.

Designer probiotics: Opening the new horizon in diagnosis and prevention of human diseases.

Probiotic microorganisms have been used for therapeutic purposes for over a century, and recent advances in biotechnology and genetic engineering have opened up new possibilities for developing therapeutic approaches using indigenous probiotic microorganisms. Diseases are often related to metabolic and immunological factors, which play a critical role in their onset. With the help of advanced genetic tools, probiotics can be modified to produce or secrete important therapeutic peptides directly into mucosal sites, increasing their effectiveness. One potential approach to enhancing human health is through the use of designer probiotics, which possess immunogenic characteristics. These genetically engineered probiotics hold promise in providing novel therapeutic options. In addition to their immunogenic properties, designer probiotics can also be equipped with sensors and genetic circuits, enabling them to detect a range of diseases with remarkable precision. Such capabilities may significantly advance disease diagnosis and management. Furthermore, designer probiotics have the potential to be used in diagnostic applications, offering a less invasive and more cost-effective alternative to conventional diagnostic techniques. This review offers an overview of the different functional aspects of the designer probiotics and their effectiveness on different diseases and also, we have emphasized their limitations and future implications. A comprehensive understanding of these functional attributes may pave the way for new avenues of prevention and the development of effective therapies for a range of diseases.

Microscopy based methods for characterization, drug delivery, and understanding the dynamics of nanoparticles.

Nanomedicine is an emerging field that exploits nanotechnology for the development of novel therapeutic and diagnostic modalities. Researches are been focussed in nanoimaging to develop noninvasive, highly sensitive, and reliable tools for diagnosis and visualization in nanomedical field. The application of nanomedicine in healthcare requires in-depth understanding of their structural, physical and morphological properties, internalization inside living system, biodistribution and localization, stability, mode of action and possible toxic health effects. Microscopic techniques including fluorescence-based confocal laser scanning microscopy, super-resolution fluorescence microscopy and multiphoton microscopy; optical-based Raman microscopy, photoacoustic microscopy and optical coherence tomography; photothermal microscopy; electron microscopy (transmission electron microscope and scanning electron microscope); atomic force microscopy; X-ray microscopy and, correlative multimodal imaging are recognized as an indispensable tool in material research and aided in numerous discoveries. Microscopy holds great promise in detecting the fundamental structures of nanoparticles (NPs) that determines their performance and applications. Moreover, the intricate details that allows assessment of chemical composition, surface topology and interfacial properties, molecular, microstructure, and micromechanical properties are also elucidated. With plethora of applications, microscopy-based techniques have been used to characterize novel NPs alongwith their proficient designing and adoption of safe strategies to be exploited in nanomedicine. Consequently, microscopic techniques have been extensively used in the characterization of fabricated NPs, and their biomedical application in diagnostics and therapeutics. The present review provides an overview of the microscopy-based techniques for in vitro and in vivo application in nanomedical investigation alongwith their challenges and advancement to meet the limitations of conventional methods.

Correction to "Green-Based Approach to Synthesize Silver Nanoparticles Using the Fungal Endophyte Penicillium oxalicum and Their Antimicrobial, Antioxidant, and In Vitro Anticancer Potential".

[This corrects the article DOI: 10.1021/acsomega.2c05605.].

Recent Advancements in the Formulation of Nanomaterials-Based Nanozymes, Their Catalytic Activity, and Biomedical Applications.

Nanozymes are nanoparticles with intrinsic enzyme-mimicking properties that have become more prevalent because of their ability to outperform conventional enzymes by overcoming their drawbacks related to stability, cost, and storage. Nanozymes have the potential to manipulate active sites of natural enzymes, which is why they are considered promising candidates to function as enzyme mimetics. Several microscopy- and spectroscopy-based techniques have been used for the characterization of nanozymes. To date, a wide range of nanozymes, including catalase, oxidase, peroxidase, and superoxide dismutase, have been designed to effectively mimic natural enzymes. The activity of nanozymes can be controlled by regulating the structural and morphological aspects of the nanozymes. Nanozymes have multifaceted benefits, which is why they are exploited on a large scale for their application in the biomedical sector. The versatility of nanozymes aids in monitoring and treating cancer, other neurodegenerative diseases, and metabolic disorders. Due to the compelling advantages of nanozymes, significant research advancements have been made in this area. Although a wide range of nanozymes act as potent mimetics of natural enzymes, their activity and specificities are suboptimal, and there is still room for their diversification for analytical purposes. Designing diverse nanozyme systems that are sensitive to one or more substrates through specialized techniques has been the subject of an in-depth study. Hence, we believe that stimuli-responsive nanozymes may open avenues for diagnosis and treatment by fusing the catalytic activity and intrinsic nanomaterial properties of nanozyme systems.

Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics.

Nano-oncology is a branch of biomedical research and engineering that focuses on using nanotechnology in cancer diagnosis and treatment. Nanomaterials are extensively employed in the field of oncology because of their minute size and ultra-specificity. A wide range of nanocarriers, such as dendrimers, micelles, PEGylated liposomes, and polymeric nanoparticles are used to facilitate the efficient transport of anti-cancer drugs at the target tumor site. Real-time labeling and monitoring of cancer cells using quantum dots is essential for determining the level of therapy needed for treatment. The drug is targeted to the tumor site either by passive or active means. Passive targeting makes use of the tumor microenvironment and enhanced permeability and retention effect, while active targeting involves the use of ligand-coated nanoparticles. Nanotechnology is being used to diagnose the early stage of cancer by detecting cancer-specific biomarkers using tumor imaging. The implication of nanotechnology in cancer therapy employs photoinduced nanosensitizers, reverse multidrug resistance, and enabling efficient delivery of CRISPR/Cas9 and RNA molecules for therapeutic applications. However, despite recent advancements in nano-oncology, there is a need to delve deeper into the domain of designing and applying nanoparticles for improved cancer diagnostics.

Exploration of in vitro cytotoxic and in ovo antiangiogenic activity of ethyl acetate extract of Penicillium oxalicum.

Fungal endophytes have established new paradigms in the area of biomedicine due to their ability to produce metabolites of pharmacological importance. The present study reports the in vitro cytotoxic and in ovo antiangiogenic activity of the ethyl acetate (EA) extract of Penicillium oxalicum and their chemical profiling through Gas Chromatography-Mass Spectrometry analysis. Treatment of the EA extract of P. oxalicum to the selected human breast cancer cell lines (MDA-MB-231 and MCF-7) leads to the reduced glucose uptake and increased nitric oxide production suggesting the cytotoxic activity of EA extract of P. oxalicum. Our results further show that treatment of EA extract of P. oxalicum attenuates the colony number, cell migration ability and alters nuclear morphology in both the human breast cancer cell lines. Furthermore, the treatment of EA extract of P. oxalicum mediates apoptosis by increasing the expression of BAX, P21, FADD, and CASPASE-8 genes, with increased Caspase-3 activity. Additionally, in ovo chorioallantoic membrane (CAM) assay showed that the treatment of EA extract of P. oxalicum leads to antiangiogenic activity with perturbed formation of blood vessels. Overall, our findings suggest that the EA extract of P. oxalicum show in vitro cytotoxic and antiproliferative activity against human breast cancer cell lines, and in ovo antiangiogenic activity in CAM model.

Isolation and characterization of N-(2-Hydroxyethyl)hexadecanamide from Colletotrichum gloeosporioides with apoptosis-inducing potential in breast cancer cells.

Endophytic fungi are a well-established reservoir of bioactive compounds that are pharmaceutically valuable and therefore, contribute significantly to the biomedical field. The present study aims to identify the bioactive anticancer compound from ethyl acetate extract of fungal endophyte, Colletotrichum gloeosporioides associated with the leaf of the medicinal plant Oroxylum indicum. The fatty acid amide compound N-(2-Hydroxyethyl)hexadecanamide (Palmitoylethanolamide; PEA) was identified using antioxidant activity-guided fractionation assisted with tandem liquid chromatography coupled with quadrupole time of flight mass spectrometry, Fourier transform-infrared spectroscopy, time-of-flight mass spectrometry, and nuclear magnetic resonance. In-Silico molecular docking analysis showed that PEA potentially docked to the active sites of apoptosis-inducing proteins including BAX, BCL-2, P21, and P53. Further validation was done using in vitro study that showed PEA inhibitsthe proliferation, alters nuclear morphology and attenuates the wound closure ability of MDA-MB-231 and MCF-7 cells. PEA induces apoptosis via upregulating cell-cycle arrest (P21), tumor suppression (P53), pro-apoptotic (BAX, CASPASE-8, and FADD) genes, and downregulating anti-apoptotic gene BCL-2. The upregulation of the active form of Caspase-3 was also reported. This is the first-ever report for the isolation of PEA from C. gloeosporioides with anticancer activity against human breast cancer cells and therefore holds great potential for future therapeutics.

Ethyl Acetate Extract of Colletotrichum gloeosporioides Promotes Cytotoxicity and Apoptosis in Human Breast Cancer Cells.

Fungal endophytes are known to be a paragon for producing bioactive compounds with a variety of pharmacological importance. The current study aims to elucidate the molecular alterations induced by the bioactive compounds produced by the fungal endophyte Colletotrichum gloeosporioides in the tumor microenvironment of human breast cancer cells. GC/MS analysis of the ethyl acetate (EA) extract of C. gloeosporioides revealed the presence of bioactive compounds with anticancer activity. The EA extract of C. gloeosporioides exerted potential plasmid DNA protective activity against hydroxyl radicals of Fenton's reagent. The cytotoxic activity further revealed that MDA-MB-231 cells exhibit more sensitivity toward the EA extract of C. gloeosporioides as compared to MCF-7 cells, whereas non-toxic to non-cancerous HEK293T cells. Furthermore, the anticancer activity demonstrated by the EA extract of C. gloeosporioides was studied by assessing nuclear morphometric analysis and induction of apoptosis in MDA-MB-231 and MCF-7 cells. The EA extract of C. gloeosporioides causes the alteration in cellular and nuclear morphologies, chromatin condensation, long-term colony inhibition, and inhibition of cell migration and proliferation ability of MDA-MB-231 and MCF-7 cells. The study also revealed that the EA extract of C. gloeosporioides treated cells undergoes apoptosis by increased production of reactive oxygen species and significant deficit in mitochondrial membrane potential. Our study also showed that the EA extract of C. gloeosporioides causes upregulation of pro-apoptotic (BAX, PARP, CASPASE-8, and FADD), cell cycle arrest (P21), and tumor suppressor (P53) related genes. Additionally, the downregulation of antiapoptotic genes (BCL-2 and SURVIVIN) and increased Caspase-3 activity suggest the induction of apoptosis in the EA extract of C. gloeosporioides treated MDA-MB-231 and MCF-7 cells. Overall, our findings suggest that the bioactive compounds present in the EA extract of C. gloeosporioides promotes apoptosis by altering the genes related to the extrinsic as well as the intrinsic pathway. Further in vivo study in breast cancer models is required to validate the in vitro observations.

Epigenetic manipulation for secondary metabolite activation in endophytic fungi: current progress and future directions.

Fungal endophytes have emerged as a promising source of secondary metabolites with significant potential for various applications in the field of biomedicine. The biosynthetic gene clusters of endophytic fungi are responsible for encoding several enzymes and transcriptional factors that are involved in the biosynthesis of secondary metabolites. The investigation of fungal metabolic potential at genetic level faces certain challenges, including the synthesis of appropriate amounts of chemicals, and loss of the ability of fungal endophytes to produce secondary metabolites in an artificial culture medium. Therefore, there is a need to delve deeper into the field of fungal genomics and transcriptomics to explore the potential of fungal endophytes in generating secondary metabolites governed by biosynthetic gene clusters. The silent biosynthetic gene clusters can be activated by modulating the chromatin structure using chemical compounds. Epigenetic modification plays a significant role by inducing cryptic gene responsible for the production of secondary metabolites using DNA methyl transferase and histone deacetylase. CRISPR-Cas9-based genome editing emerges an effective tool to enhance the production of desired metabolites by modulating gene expression. This review primarily focuses on the significance of epigenetic elicitors and their capacity to boost the production of secondary metabolites from endophytes. This article holds the potential to rejuvenate the drug discovery pipeline by introducing new chemical compounds.

Green-Based Approach to Synthesize Silver Nanoparticles Using the Fungal Endophyte Penicillium oxalicum and Their Antimicrobial, Antioxidant, and In Vitro Anticancer Potential.

A green-based approach for the synthesis of silver nanoparticles has gained tremendous attention in biomedical applications. Fungal endophytes have been recognized as a remarkable biological source for the synthesis of potential nanodrugs. The present study focuses on the fabrication of silver nanoparticles using the fungal endophyte Penicillium oxalicum (POAgNPs) associated with the leaf of the Amoora rohituka plant. Sharp UV-visible spectra at 420 nm appeared due to the surface plasmon resonance of POAgNPs and the reduction of silver salt. FT-IR analysis revealed the presence of functional groups of bioactive compounds of P. oxalicum responsible for the reduction of silver salt and validated the synthesis of POAgNPs. A high degree of crystallinity was revealed through XRD analysis, and microscopy-based characterizations such as AFM, TEM, and FESEM showed uniformly distributed, and spherically shaped nanoparticles. Furthermore, POAgNPs showed a potential inhibitory effect against bacterial and fungal strains of pathogenic nature. POAgNPs also exhibited potential antioxidant activity against the synthetically generated free radicals such as DPPH, superoxide, hydroxyl, and nitric oxide with EC50 values of 9.034 ± 0.449, 56.378 ± 1.137, 34.094 ± 1.944, and 61.219 ± 0.69 µg/mL, respectively. Moreover, POAgNPs exhibited cytotoxic potential against the breast cancer cell lines, MDA-MB-231 and MCF-7 with IC50 values of 20.080 ± 0.761 and 40.038 ± 1.022 µg/mL, respectively. POAgNPs showed anticancer potential through inhibition of wound closure and by altering the nuclear morphology of MDA-MB-231 and MCF-7 cells. Further anticancer activity revealed that POAgNPs induced apoptosis in MDA-MB-231 and MCF-7 cells by differential expression of genes related to apoptosis, tumor suppression, and cell cycle arrest and increased the level of Caspase-3. The novel study showed that P. oxalicum-mediated silver nanoparticles exhibit potential biological activity, which can be exploited as nanodrugs in clinical applications.

Effect of Urinary Trypsin Inhibitor (Ulinastatin) Therapy in COVID-19.

Purpose: End-organ damage in coronavirus disease-2019 (COVID-19) is linked to "cytokine storm" and excessive release of inflammatory mediators. Various novel therapies have been used in COVID-19 including urinary trypsin inhibitor therapy. This study explores the efficacy of ulinastatin in COVID-19. Materials and methods: We retrieved the medical records of patients admitted during one month and did a propensity score analysis to create matched treatment and control groups. We analyzed these groups and the outcomes were presented with appropriate statistics. Survival curve was prepared to compare the survival effect of ulinastatin therapy at the end of hospitalization, among both the groups. Results: A total of 736 patients were admitted, and after adjusting the data with propensity score matching, 55 cases were selected by the system. On the final outcome analysis, we found that intensive care unit (ICU) length of stay [median (interquartile range) days 3 (3.5-7.8) vs 2 (0-4); p-value 0.28] in control vs intervention groups, and in hospital mortality (odds ratio: 0.491, CI 95%: 0.099-2.44, p-value 0.435) were not statistically different among the groups. In survival plot analysis also, there was no statistical difference (p-value 0.414) among both the groups.Conclusion: In this retrospective study, we conclude that the final outcome of the ICU length of stay, and overall, in hospital mortality were not different among both the groups. Hence, adequately powered randomized control trials are urgently required to confirm any benefit of ulinastatin therapy in COVID-19 treatment. How to cite this article: Jain A, Kasliwal R, Jain SS, Jain R, Gupta D, Gupta P, et al. Effect of Urinary Trypsin Inhibitor (Ulinastatin) Therapy in COVID-19. Indian J Crit Care Med 2022;26(6):696-703.

Assessment of Biological Activities of Fungal Endophytes Derived Bioactive Compounds Isolated from Amoora rohituka.

Fungal endophytes have remarkable potential to produce bioactive compounds with numerous pharmacological significance that are used in various disease management and human welfare. In the current study, a total of eight fungal endophytes were isolated from the leaf tissue of Amoora rohituka, and out of which ethyl acetate (EA) extract of Penicillium oxalicum was found to exhibit potential antioxidant activity against DPPH, nitric oxide, superoxide anion and hydroxyl free radicals with EC50 values of 178.30 ± 1.446, 75.79 ± 0.692, 169.28 ± 0.402 and 126.12 ± 0.636 µg/mL, respectively. The significant antioxidant activity of EA extract of P. oxalicum is validated through highest phenolic and flavonoid content, and the presence of unique bioactive components observed through high-performance thin layer chromatography (HPTLC) fingerprinting. Moreover, EA extract of P. oxalicum also displayed substantial anti-proliferative activity with IC50 values of 56.81 ± 0.617, 37.24 ± 1.26 and 260.627 ± 5.415 µg/mL against three cancer cells HuT-78, MDA-MB-231 and MCF-7, respectively. Furthermore, comparative HPTLC fingerprint analysis and antioxidant activity of P. oxalicum revealed that fungal endophyte P. oxalicum produces bioactive compounds in a host-dependent manner. Therefore, the present study signifies that fungal endophyte P. oxalicum associated with the leaf of A. rohituka could be a potential source of bioactive compounds with antioxidant and anticancer activity.

Fungal Endophytes: an Accessible Source of Bioactive Compounds with Potential Anticancer Activity.

Endophytes either be bacteria, fungi, or actinomycetes colonize inside the tissue of host plants without showing any immediate negative effects on them. Among numerous natural alternative sources, fungal endophytes produce a wide range of structurally diverse bioactive metabolites including anticancer compounds. Considering the production of bioactive compounds in low quantity, genetic and physicochemical modification of the fungal endophytes is performed for the enhanced production of bioactive compounds. Presently, for the treatment of cancer, chemotherapy is majorly used, but the side effects of chemotherapy are of prime concern in clinical practices. Also, the drug-resistant properties of carcinoma cells, lack of cancer cells-specific medicine, and the side effects of drugs are the biggest obstacles in cancer treatment. The interminable requirement of potential drugs has encouraged researchers to seek alternatives to find novel bioactive compounds, and fungal endophytes seem to be a probable target for the discovery of anticancer drugs. The present review focuses a comprehensive literature on the major fungal endophyte-derived bioactive compounds which are presently been used for the management of cancer, biotic factors influencing the production of bioactive compounds and about the challenges in the field of fungal endophyte research.

Bioprospecting of fungal endophytes from Oroxylum indicum (L.) Kurz with antioxidant and cytotoxic activity.

Oroxylum indicum (L.) Kurz, a medicinal plant, shows numerous pharmacological properties which may be attributed to the bioactive compounds produced by O. indicum or due to associated endophytes. In the present study, leaf of O. indicum was evaluated for the presence of associated fungal endophytes, and antioxidant and cytotoxic activities of bioactive compounds produced from them. Using culture-dependent approach, eight fungal endophytes belonging to five different genera were identified. Two endophytes Daldinia eschscholtzii and Ectophoma multirostrata have been reported for the first time from the leaf of O. indicum plant. High-performance thin-layer chromatography (HPTLC) of ethyl acetate (EA) extract of isolated fungal endophytes showed a distinct fingerprinting profile in EA extract of Colletotrichum gloeosporioides. Among identified endophytes, EA extract of C. gloeosporioides showed significant antioxidant activity against DPPH free radical, superoxide anion radical, nitric oxide radical and hydroxyl radical with EC50 values of 22.24±1.302 µg/mL, 67.46±0.576 µg/mL, 80.10±0.706 µg/mL and 61.55±1.360 µg/mL, respectively. EA extract of C. gloeosporioides exhibited potential cytotoxicity against HCT116, HeLa and HepG2 cancer cell lines with IC50 values of 76.59 µg/mL, 176.20 µg/mL and 1750.70 µg/mL, respectively. A comparative HPTLC fingerprinting and the antioxidant activity of C. gloeosporioides associated with two different hosts (leaf of O. indicum and dead twigs of other plant) showed that C. gloeosporioides produces bioactive compounds in a host-dependent manner.

The Comparison of Inflation of Cuff with 1% Propofol, 4% Lignocaine, or 0.9% Saline on Laryngotracheal Morbidity.

Background and Aim: While administering general anesthesia requiring endotracheal intubation, it is a common practice to inflate the cuff with air. Continuous pressure exerted by cuff on mucosa may lead to postoperative complaints such as sore throat, cough, and dysphagia, which are very disturbing to the patient. Hence, we hypothesized that inflation of cuff with propofol may reduce the incidence of these complications as a result of cushioning effect as well as non-diffusion of nitrous oxide into it. Our aim was to compare the effects of inflation of endotracheal tube cuff with 0.9% saline, 4% lignocaine, and 1% propofol on the incidence of postoperative morbidity in terms of cough, sore throat, dysphonia, and dysphagia with general anesthesia using nitrous oxide. Methods: Patients scheduled for elective surgery under general anesthesia were randomly allocated into four equal groups of thirty each as per cuff inflation media: air (Group A), 0.9% saline (Group S), 4% lidocaine (Group L), and 1% propofol (Group P). The incidence of cough was noted at 15, 30 and 60 min after extubating. The occurrence and severity of postoperative sore throat (POST) was evaluated at 2, 6, and 24 h after extubating. Results: The incidence of cough was maximum in Group A and minimum in Group P (P < 0.05). The occurrence of POST was highest in Group A, followed by Group S and Group L, and least in Group P. The hemodynamic parameters were comparable with no statistical difference in all the four groups (P < 0.05). Conclusion: The intracuff 1% propofol is superior to 4% xylocaine and normal saline in the prevention of cough and sore throat postoperatively, whereas inflation of cuff with air leads to maximum incidence of these complications.

A Comparative Study of Dexmedetomidine versus Nalbuphine Used as an Adjuvant to Chloroprocaine for Daycare Surgeries Performed under Subarachnoid Block.

Backgrounds and Aims: Nalbuphine or dexmedetomidine when used as an adjuvant to local anesthetic agents may alter the characteristics of subarachnoid block. The study aimed to compare the effect of adding these drugs as an adjuvant to chloroprocaine for spinal anesthesia. Settings and Design: This prospective, randomized, double-blind study was conducted at a tertiary care center. Materials and Methods: After obtaining permission from the institutional ethical committee and informed patient consent, patients scheduled for surgeries under subarachnoid block were randomized into three groups of 50 each: Group C: Injection 1% chloroprocaine 40 mg (4 mL) with 1 mL normal saline, Group DC: injection 1% chloroprocaine 40 mg (4 mL) with dexmedetomidine 10 µg diluted to 1 mL in normal saline, and Group NC: injection 1% chloroprocaine 40 mg (4 mL) with nalbuphine 0.4 mg diluted to 1 mL in normal saline. Onset, peak, duration, and time to complete regression of sensory and motor blockade were noted. Side effects, if any, were noted and managed appropriately. Statistical Analysis: Qualitative data were analyzed using Chi-square test and quantitative data were analyzed using Student's t-test and two-sided Mann-Whitney U-test. P < 0.05 was considered statistically significant. Results: Group DC had prolonged time to onset, duration, and complete regression of sensory and motor block compared to Group NC and Group C (P < 0.001). Hemodynamic parameters, sedation score, and side effects were comparable in all groups. Conclusion: Thus, nalbuphine is a better adjuvant to chloroprocaine than dexmedetomidine when administered intrathecally for daycare surgeries performed under spinal anesthesia.

Mass Spectrometry-Based Technology and Workflows for Studying the Chemistry of Fungal Endophyte Derived Bioactive Compounds.

Bioactive compounds have gained substantial attention in research and have conferred great advancements in the industrial and pharmacological fields. Highly diverse fungi and their metabolome serve as a big platform to be explored for their diverse bioactive compounds. Omics tools coupled with bioinformatics, statistical, and well-developed algorithm tools have elucidated immense knowledge about fungal endophyte derived bioactive compounds. Further, these compounds are subjected to chromatography-gas chromatography and liquid chromatography (LC), spectroscopy-nuclear magnetic resonance (NMR), and "soft ionization" technique-matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) based analytical techniques for structural characterization. The mass spectrometry (MS)-based approach, being highly sensitive, reproducible, and reliable, produces quick and high-profile identification. Coupling these techniques with MS has resulted in a descriptive account of the identification and quantification of fungal endophyte derived bioactive compounds. This paper emphasizes the workflows of the above-mentioned techniques, their advancement, and future directions to study the unraveled area of chemistry of fungal endophyte-derived bioactive compounds.

A randomized comparison between pulse pressure variation and central venous pressure in patients undergoing renal transplantation.

Background and Aims: Intraoperative fluid management is important in renal transplant recipients with end-stage renal disease. Conventionally, central venous pressure (CVP) has been used to guide perioperative fluid administration but with high incidence of poor graft outcome. There is a requirement of reliable parameter to guide the fluid therapy in these patients so as to minimize the perioperative complications and improve the outcome. Hence, this study was conducted. Material and Methods: This prospective study included 75 patients of chronic kidney disease undergoing renal transplantation. Patients were divided into two groups. Group A (control group): Intraoperative fluids were guided by CVP; Group B: Intraoperative fluids were guided by pulse pressure variation (PPV). Primary outcome measure of this study was incidence of delayed graft functioning, i.e., need of hemodialysis within 7 days of renal transplant. Secondary outcome measures were incidence of perioperative hypotension, post-transplant pulmonary edema, tissue edema, and lactic acidosis. Results: Total amount of fluid before reperfusion was significantly greater in the control group (P = 0.005). However, the total amount of fluid required at the end of surgery was comparable. Delayed graft functioning was seen only in CVP group, although it was not statistically significant. The postoperative tissue edema was more in CVP group (P = 0.03). The postoperative nausea and vomiting, pulmonary edema, and mechanical ventilation were more in CVP group but not statistically significant. Increase in lactate value was more in CVP group. Conclusion: Perioperative fluid guidance by PPV is better than central venous pressure in renal transplant patients.