Deciphering the landscape of triple negative breast cancer from microenvironment dynamics and molecular insights to biomarker analysis and therapeutic modalities.

Triple negative breast cancer (TNBC) displays a notable challenge in clinical oncology due to its invasive nature which is attributed to the absence of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor (HER-2). The heterogenous tumor microenvironment (TME) of TNBC is composed of diverse constituents that intricately interact to evade immune response and facilitate cancer progression and metastasis. Based on molecular gene expression, TNBC is classified into four molecular subtypes: basal-like (BL1 and BL2), luminal androgen receptor (LAR), immunomodulatory (IM), and mesenchymal. TNBC is an aggressive histological variant with adverse prognosis and poor therapeutic response. The lack of response in most of the TNBC patients could be attributed to the heterogeneity of the disease, highlighting the need for more effective treatments and reliable prognostic biomarkers. Targeting certain signaling pathways and their components has emerged as a promising therapeutic strategy for improving patient outcomes. In this review, we have summarized the interactions among various components of the dynamic TME in TNBC and discussed the classification of its molecular subtypes. Moreover, the purpose of this review is to compile and provide an overview of the most recent data about recently discovered novel TNBC biomarkers and targeted therapeutics that have proven successful in treating metastatic TNBC. The emergence of novel therapeutic strategies such as chemoimmunotherapy, chimeric antigen receptor (CAR)-T cells-based immunotherapy, phytometabolites-mediated natural therapy, photodynamic and photothermal approaches have made a significant positive impact and have paved the way for more effective interventions.

Myco-nanotechnological approach to synthesize gold nanoparticles using a fungal endophyte,Penicillium oxalicum, and unravelling its antibacterial activity and anti-breast cancer role via metabolic reprogramming.

The present study has been designed to fabricate fungal endophyte-assisted gold nanoparticles (AuNPs) and elucidate their anti-breast cancer potential. The aqueous extract of fungal endophytePenicillium oxalicum(PO), associated with the medicinal plantAmoora rohituka, was used for the fabrication of AuNPs (POAuNPs). Physico-chemical characterization using Ultraviolet-visible spectroscopy, Fourier transform infrared, X-ray diffraction, Dynamic light scattering, Zeta potential, Transmission electron microscopy and Field emission scanning electron microscopy analysis revealed stable, uniform distribution, spherical shape and crystalline nature of POAuNPs with a size range of 3-46 nm. Furthermore, the POAuNPs potentially inhibited the growth of pathogenic bacterial strainsEscherichia coliandStaphylococcus aureus. The synthesized POAuNPs have shown potential antioxidant effects against 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and nitric oxide (NO) radical scavenging assays with an EC50value of 8.875 ± 0.082, 52.593 ± 2.506 and 43.717 ± 1.449 µg mL-1, respectively. Moreover, the value of EC50for the total antioxidant capacity of POAuNPs was found to be 23.667 ± 1.361 µg mL-1. The cell viability of human breast cancer cells, MDA-MB-231 and MCF-7, was found to be reduced after treatment with POAuNPs, and IC50values were found to be 19.753 ± 0.640 and 35.035 ± 0.439 µg mL-1, respectively. Further,in vitrobiochemical assays revealed that POAuNPs induces metabolic reprogramming in terms of reduced glucose uptake, increased lactate dehydrogenase (LDH) release and, disruption of oxidative balance through depletion of glutathione levels, increased nitric oxide (NO) and lipid peroxidation levels as a possible pathway to suppress human breast cancer cell proliferation. Apoptosis-specific nuclear modulations induced by POAuNPs in human breast cancer cells were validated through 4',6-diamidino-2-phenylindole (DAPI) nuclear staining. The present investigation thus attempts to show the first ever fabrication of AuNPs using an aqueous extract ofP. oxalicumassociated withA. rohituka. The results revealed unique physico-chemical characteristics of mycogenic AuNPs, and screening their effect against breast cancer via metabolic reprogramming and induction of apoptosis thus adds great significance for cancer therapeutics, suggesting further exploration to develop nanotherapeutic drugs.

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

[This corrects the article DOI: 10.1371/journal.pone.0264673.].

Sustainable Synthesis of Novel Green-Based Nanoparticles for Therapeutic Interventions and Environmental Remediation.

The advancement in nanotechnology has completely revolutionized various fields, including pharmaceutical sciences, and streamlined the potential therapeutic of many diseases that endanger human life. The synthesis of green nanoparticles by biological processes is an aspect of the newly emerging scientific field known as "green nanotechnology". Due to their safe, eco-friendly, nontoxic nature, green synthesis tools are better suited to produce nanoparticles between 1 and 100 nm. Nanoformulation of different types of nanoparticles has been made possible by using green production techniques and commercially feasible novel precursors, such as seed extracts, algae, and fungi, that act as potent reducing, capping, and stabilizing agents. In addition to this, the biofunctionalization of nanoparticles has also broadened its horizon in the field of environmental remediation and various novel therapeutic innovations including wound healing, antimicrobial, anticancer, and nano biosensing. However, the major challenge pertaining to green nanotechnology is the agglomeration of nanoparticles that may alter the surface topology, which can affect biological physiology, thereby contributing to system toxicity. Therefore, a thorough grasp of nanoparticle toxicity and biocompatibility is required to harness the applications of nanotechnology in therapeutics.

Correlation of oxygenation indices in invasive mechanical ventilated adult patients.

BACKGROUND: Mechanical ventilation is essential for managing acute respiratory failure, but traditional methods of assessing oxygenation, like the PaO2/FiO2 ratio, pose challenges due to invasiveness and cost. OBJECTIVE: This single-centre prospective observational study aimed to assess the potential of the non-invasive Oxygen Saturation Index (OSI), utilising SpO2 measurements, to diagnose hypoxemia in mechanically ventilated adults. The study sought to establish correlations between OSI, oxygenation index (OI), PaO2/FiO2 ratio and SpO2/FiO2 ratio. METHODS: From August 2022 to July 2023, data was collected from 1055 mechanically ventilated intensive care unit patients. Statistical analysis included correlation tests, receiver operating curve (ROC) analysis and cut-off value determination for hypoxemia diagnosis. RESULTS: We found that the P/F ratio had a statistically significant negative correlation with OI (correlation coefficient -0.832, P value: 0.000 in hypoxemic group and correlation coefficient -0.888, P value: 0.000 in the non-hypoxemic group), and OSI (correlation coefficient -0.746, P value: 0.000 in hypoxemic group and correlation coefficient -0.629, P value: 0.000 in non-hypoxemic group) and has a positive correlation with P/F ratio (correlation coefficient 0.92, P value: 0.000 in hypoxemic group and correlation coefficient -0.67, P value: 0.000 in non-hypoxemic group). OI and OSI had a statistically significant correlation (correlation coefficient 0.955, P value: 0.000 in hypoxemic group and correlation coefficient 0.815, P value: 0.000 in non-hypoxemic group). on ROC analysis P/F ratio was the most accurate in predicting hypoxia followed by OI and OSI. with a cut-off value, of OI being 7.07, and that for OSI being 3.90, at an 80% sensitivity level to diagnose hypoxemia. CONCLUSION: OSI can serve as a dependable surrogate for OI, simplifying ARDS severity assessment. The P/F ratio is the most accurate predictor of hypoxia. Further research, especially in larger multicentre studies, is needed to validate these findings and explore the long-term clinical implications of using OSI for oxygenation monitoring in mechanically ventilated patients.

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.

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.

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.].

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.

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.

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.

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.

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.

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.

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.