Homoharringtonine: updated insights into its efficacy in hematological malignancies, diverse cancers and other biomedical applications.

HHT has emerged as a notable compound in the realm of cancer treatment, particularly for hematological malignancies. Its multifaceted pharmacological properties extend beyond traditional applications, warranting an extensive review of its mechanisms and efficacy. This review aims to synthesize comprehensive insights into the efficacy of HHT in treating hematological malignancies, diverse cancers, and other biomedical applications. It focuses on elucidating the molecular mechanisms, therapeutic potential, and broader applications of HHT. A comprehensive search for peer-reviewed papers was conducted across various academic databases, including ScienceDirect, Web of Science, Scopus, American Chemical Society, Google Scholar, PubMed/MedLine, and Wiley. The review highlights HHT's diverse mechanisms of action, ranging from its role in leukemia treatment to its emerging applications in managing other cancers and various biomedical conditions. It underscores HHT's influence on cellular processes, its efficacy in clinical settings, and its potential to alter pathological pathways. HHT demonstrates significant promise in treating various hematological malignancies and cancers, offering a multifaceted approach to disease management. Its ability to impact various physiological pathways opens new avenues for therapeutic applications. This review provides a consolidated foundation for future research and clinical applications of HHT in diverse medical fields.

Molecular identification and phylogenetic analysis of chikungunya virus among dengue-negative patients in Kolkata, India.

Dengue and chikungunya are co-circulating vector-borne diseases that share a significant number of clinical symptoms. To identify variables to aid physicians in making rapid and effective diagnostic decisions, we performed molecular diagnosis of the chikungunya virus and examined the clinical manifestations of chikungunya cases to identify the prevalence among dengue-negative individuals in Kolkata. Dengue suspected patients' samples were collected during January 2020-December 2021 and Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) methods have been performed to confirm the prevalence of chikungunya infection among dengue-negative patients. By performing phylogenetic analysis, comparing clinical classifications, identifying disease aetiology using clinical and laboratory factors, and evaluating the time course of several clinical variables, we have evaluated the clinical manifestations linked to dengue and chikungunya virus infections. Chikungunya infection was found in 15.1% and 6.3% of the 635 dengue-negative patients, as determined by ELISA and RT-PCR, respectively. Arthritis and myalgia were more common in chikungunya-infected patients at the time of hospital admission while conjunctivitis, photosensitivity, arthralgia, Anorexia, fatigue, retro-orbital pain, vomiting, dermatitis, or swollen glands were significantly presented as an overlapping symptom. Although dengue and chikungunya infections have significant clinical overlap, basic clinical and laboratory criteria can predict these diseases at presentation for proper management. Effective management enables doctors to treat and care for patients properly and contributes to the development of control measures for these infections in a medical setting.

Flame self-interactions in MILD combustion of homogeneous and inhomogeneous mixtures.

Flame self-interaction (FSI) events in Moderate or Intense Low-Oxygen Dilution (MILD) combustion of homogeneous and inhomogeneous mixtures of methane and oxidiser have been analysed using three-dimensional Direct Numerical Simulations (DNS). The simulations have been conducted at the same global equivalence ratio ( ⟨ ϕ ⟩ = 0.8 ) for different levels of O 2 concentration (dilution) and initial turbulence intensities. It has been reported that both homogeneous and inhomogeneous mixture MILD combustion cases exhibit significant occurrences of FSI events, with the peak frequency of FSI events occurring towards the burned gas side in all cases. Moreover, the frequency of FSI events increases with increasing dilution level and turbulence intensity, but the presence of mixture inhomogeneity leads to a reduction in total FSI events. In all cases, the cylindrical FSI topologies (i.e. tunnel formation and tunnel closure) were found to have a higher likelihood of occurrence compared to spherical FSI topologies (i.e. unburned and burned gas pockets). The geometries of FSI topologies were also analysed using the mean and Gaussian curvatures. It has been shown that the inward propagating spherical FSI topologies (i.e. unburned gas pockets) are associated with negative mean curvature, while outward propagating spherical FSI topologies (i.e. burned gas pockets) are associated with positive mean curvature. Moreover, tunnel formation (tunnel closure) FSI topologies predominantly exhibit either elliptic geometries with positive (negative) mean curvature or hyperbolic saddle geometries with negative (positive) mean curvature. It has been shown for the first time in MILD combustion that the mean values of kinematic restoration and dissipation terms in the transport equation of the magnitude of the reaction progress variable conditional upon the reaction progress variable tend to cancel each other in the vicinity of the critical points associated with cylindrical topologies. Thus, the singular contributions in these terms, which are obtained from analytical descriptions in the vicinity of tunnel formation and tunnel closure topologies, do not affect the balance equation of the magnitude of the gradient of the reaction progress variable. Consequently, there is no need for a separate model treatment for singularities in modelling approaches based on the magnitude of the gradient of the reaction progress variable. The FSI events in the reaction dominated and propagating flame regions of MILD combustion have also been analysed for the first time. It has been found that more FSI events occur in the reaction dominated region, particularly towards the burned gas side. However, the majority of spherical FSI topologies are found in the propagating flame region. The findings from this study indicate that turbulence intensity, dilution level and mixture inhomogeneity effects need to be considered in any attempt to extend flame surface-based modelling approaches to MILD combustion.

Progression of retinal choroidal neovascularization by latent human cytomegalovirus infection and immunological signaling among neonatal patients admitted to tertiary care hospital.

Choroidal neovascularization (CNV) is a serious condition that affects the retina, causing partial or complete blindness in people of different ages. While CNV is a common occurrence in various chorioretinopathies, research on its occurrence in neonates is limited. Human cytomegalovirus (HCMV) is a significant health threat to neonates, with a strong association with retinal angiogenesis. However, there has been limited investigation into HCMV-associated CNV progression. In this article, we extensively studied the expression of different inflammatory cytokines and chemokines during latent HCMV-associated retinal neovascularization. Our research found that HCMV-induced CNV progression was significantly prominent in the presence of AT2R-dependent angiogenesis (p < 0.001), whereas in the absence of HCMV, AT1R-dependent CCL-5-mediated angiogenesis was documented. We also observed significant increases in CCL-19, CCL-21 chemokine responses, followed by CCR-7 chemokine receptor activation (p < 0.001) in HCMV-induced CNV patients compared to HCMV non-induced CNV groups. Furthermore, significant changes in predictive chemokine markers of HCMV-induced CNV were positively correlated with HCMV viremia. These immunological alterations ultimately lead to the switching of NFκB canonical and noncanonical pathways, respectively, in HCMV-induced neonatal CNV and HCMV non-induced CNV. This clinical observation presents a novel hypothesis that ocular HCMV latency poses a noteworthy risk factor for the progression of retinal neovascularization through a distinctive immunological signaling pathway. The current study represents the first of its kind to report on this association, which may have significant implications for the clinical management of patients with ocular HCMV.

Anticancer activity and other biomedical properties of ß-sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches.

Sterols, including ß-sitosterol, are essential components of cellular membranes in both plant and animal cells. Despite being a major phytosterol in various plant materials, comprehensive scientific knowledge regarding the properties of ß-sitosterol and its potential applications is essential for scholarly pursuits and utilization purposes. ß-sitosterol shares similar chemical characteristics with cholesterol and exhibits several pharmacological activities without major toxicity. This study aims to bridge the gap between phytochemistry and current pharmacological evidence of ß-sitosterol, focusing on its anticancer activity and other biomedical properties. The goal is to provide a comprehensive understanding of ß-sitosterol's potential for future translational approaches. A thorough examination of the literature was conducted to gather relevant information on the biological properties of ß-sitosterol, particularly its anticancer therapeutic potential. Various databases were searched, including PubMed/MedLine, Scopus, Google Scholar, and Web of Science using appropriate keywords. Studies investigating the effects of ß-sitosterol on different types of cancer were analyzed, focusing on mechanisms of action, pharmacological screening, and chemosensitizing properties. Modern pharmacological screening studies have revealed the potential anticancer therapeutic properties of ß-sitosterol against various types of cancer, including leukemia, lung, stomach, breast, colon, ovarian, and prostate cancer. ß-sitosterol has demonstrated chemosensitizing effects on cancer cells, interfering with multiple cell signaling pathways involved in proliferation, cell cycle arrest, apoptosis, survival, metastasis invasion, angiogenesis, and inflammation. Structural derivatives of ß-sitosterol have also shown anti-cancer effects. However, research in the field of drug delivery and the detailed mode of action of ß-sitosterol-mediated anticancer activities remains limited. ß-sitosterol, as a non-toxic compound with significant pharmacological potential, exhibits promising anticancer effects against various cancer types. Despite being relatively less potent than conventional cancer chemotherapeutics, ß-sitosterol holds potential as a safe and effective nutraceutical against cancer. Further comprehensive studies are recommended to explore the biological properties of ß-sitosterol, including its mode of action, and develop novel formulations for its potential use in cancer treatment. This review provides a foundation for future investigations and highlights the need for further research on ß-sitosterol as a potent superfood in combating cancer.

Unraveling lipid peroxidation-mediated regulation of redox homeostasis for sustaining plant health.

Lipid peroxidation (LPO) is a complex process that, depending on the context, can either result in oxidative injury or promote redox homeostasis. LPO is a series of reactions in which polyunsaturated fatty acids are attacked by free radicals that result in the synthesis of lipid peroxides. LPO can alter membrane fluidity and operation and produce secondary products that amplify oxidative stress. LPO can activate cellular signaling pathways that promote antioxidant defense mechanisms that provide oxidative stress protection by elevating antioxidant enzyme action potentials. Enzymatic and nonenzymatic mechanisms tightly regulate LPO to prevent excessive LPO and its adverse consequences. This article emphasizes the dual nature of LPO as a mechanism that can both damage cells and regulate redox homeostasis. In addition, it also highlights the major enzymatic and nonenzymatic mechanisms that tightly regulate LPO to prevent excessive oxidative damage. More importantly, it emphasizes the importance of understanding the cellular and biochemical complexity of LPO for developing strategies targeting this process for efficient management of plant stress.

Spermine induced endogenous signal ameliorates osmotic stress in Lens culinaris.

The present study evaluates the alleviation of polyethylene glycol (PEG) mediated osmotic stress by exogenous spermine (SP) application on seeds of Lens culinaris. Seeds were soaked overnight with SP (0.05 M) and PEG (10%) separately. Third set was prepared by combined treatment with SP (0.05 M) and PEG (10%). Further, various physiological parameters, defense enzymes, phenol, flavonoid, nitric oxide (NO), proline content, chromosomal abnormality studies etc. was conducted after 5 days of incubation. PEG application significantly hampered the seed germination, root length, shoot length, relative water content and vigour index. Application of PEG induced electrolytic leakage in root cells. PEG application also significantly reduced the activities of different defense parameters viz. peroxidase, polyphenol oxidase, phenylalanine ammonia lyase and ß-1,3 glucanase, total phenol and flavonoid accumulation over control. Reactive oxygen species, lipid peroxidation, cell death was found significantly high in PEG treated sets. However, NO level has been significantly decreased by PEG treatment. Cytological studies showed reduced mitotic index and highest abnormalities under osmotic stress. Contrary to that, application of SP either alone or in combination with PEG showed improved responses of aforesaid defense parameters compared to control and solely PEG treated sets. Interestingly, cytological abnormalities were also reduced in SP treated roots. Overall, these results suggests that SP application on seeds reduced the PEG induced damage and intricately improved the defense mechanisms which might help to fight against oxidative stress.

Ethnopharmacological Potential of Phytochemicals and Phytogenic Products against Human RNA Viral Diseases as Preventive Therapeutics.

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.

Surface topologies and self interactions in reactive and nonreactive Richtmyer-Meshkov instability.

The reactive Richtmyer-Meshkov instability (RMI) exhibits strong wrinkling of a reactive flame front after an interaction with a shock wave. High levels of deformation and wrinkling can cause the flame surface to intersect with itself, leading to the events of flame self interactions (FSI). As FSI can have a significant influence on the development and topology of the flame surface, it should be considered an important factor affecting the burning characteristics of the flame. The topological structure and statistics of FSI are analyzed using data from high-fidelity simulations of a planar shock wave interacting with a statistically planar hydrogen/air flame for stoichiometric, lean and nonreactive gas mixtures. FSI events are detected by searching for critical points in the field of the reaction progress variable c and divided into the following topological categories: burned gas mixture pocket (BP), unburned gas mixture pocket (UP), tunnel formation (TF) and tunnel closure (TC). It is found that reactivity and flame thickness are decisive factors, influencing the frequency and topological distribution of the detected FSI events. While in early RMI-stages the FSI is found to be mainly dependent on the flame thickness, later stages are heavily influenced by the reactivity, as high reactivity quickly burns out emerging wrinkled structures (in the stoichiometric case) leading to massively reduced levels of FSI. The findings are further supported by the results from the nonreactive case, which at later stages of the RMI closely resembles the less reactive lean case. Analysis of the topology distribution over time and conditioned over c, reveals further differences between the lean and stoichiometric case, as the strong wrinkling and mixing encountered with the lean case facilitates the build up of many pocket-type and tunnel-type interactions throughout the wrinkled flame front. For the stoichiometric case, mainly tunnel-type and unburned pocket topologies are found in the narrow flame funnels extending into the burned gas.

Bioinoculant mediated regulation of signalling cascades in various stress responses in plants.

Bio-inoculation involves the association of plant with some beneficial microorganisms, and among these microbiotas, those bacteria which can promote plant growth and development are known as Plant Growth Promoting Rhizobacteria (PGPR). It can help a plant directly or indirectly, which includes root development, biological nitrogen (N2) fixation, stress tolerance, cell division and elongation, solubilization of Zinc, Phosphate, Potassium, soil health improvement and many more. PGPR have gained attention as it can be used as biofertilizers and helpful in bioremediation techniques, which in turn can reduce the chemical dependency in agriculture. PGPR mediated plant growth and stress management is developed by the virtue of the interaction of plant and microbial signalling pathways. On the other hand, environmental stresses are something to which a plant is always exposed irrespective of other factors. The present review is all about the better understanding of the convergence strategies of these signalling molecules and the ambiguities of signalling activities occurring in the host due to the interaction with PGPR under environmental stressed conditions.

A comparative analysis depicting the disease characteristics and phylogenetic signature of human cytomegalovirus infection in Human Immunodeficiency Virus 1 seropositive patients with end-organ retinitis and gastro-enteric diseases.

During advanced HIV infection, Human Cytomegalovirus (HCMV) has been proven to produce devitalizing end-organ diseases (EOD). The interactive co-existence of HIV and HCMV has been reported by many researchers and has been suggested to be linked with a more aggressive disease state. This study has been designed to bring forward an assessment of the clinical risk factors capable of defining the conditions of HCMV induced retinitis and gastro-enteric diseases among HIV1 seropositive patients. We also intended to analyse the phylogenetic variation if any, among the infecting virus types inducing the two separate clinical conditions. The patients were arranged in three different groups; (Group 1 with 26 individuals and group 2 and group 3 with 25 individuals each) based on their current status of HIV and HCMV infections. Serum ELISA, qualitative and quantitative detection of HCMV DNA, Real time mRNA expression study, sequencing, and phylogenetic analysis were performed. All statistical analyses and graphs were exercised using relevant software. We found that in HIV patients with HCMV induced end-organ diseases the components of the CXCL9, 10, 11-CXCR3 chemokine pathway is highly expressed with significant differences existing among patients with retinitis and gastrointestinal disease. We found that the gL gene sequences from the retinitis (HR) group clustered almost separately from that of the gastroenteritis (HG) group in the phylogenetic tree. It may be suggested that a form of natural selection pressure is working on the clinical HCMV strains creating a slight divergence in their phylogenetic lineage thereby helping them adapt to the particular tissue microenvironment they are colonizing.

Entropy Generation during Head-On Interaction of Premixed Flames with Inert Walls within Turbulent Boundary Layers.

The statistical behaviours of different entropy generation mechanisms in the head-on interaction of turbulent premixed flames with a chemically inert wall within turbulent boundary layers have been analysed using Direct Numerical Simulation data. The entropy generation characteristics in the case of head-on premixed flame interaction with an isothermal wall is compared to that for an adiabatic wall. It has been found that entropy generation due to chemical reaction, thermal diffusion and molecular mixing remain comparable when the flame is away from the wall for both wall boundary conditions. However, the wall boundary condition affects the entropy generation during flame-wall interaction. In the case of isothermal wall, the entropy generation due to chemical reaction vanishes because of flame quenching and the entropy generation due to thermal diffusion becomes the leading entropy generator at the wall. By contrast, the entropy generation due to thermal diffusion and molecular mixing decrease at the adiabatic wall because of the vanishing wall-normal components of the gradients of temperature and species mass/mole fractions. These differences have significant effects on the overall entropy generation rate during flame-wall interaction, which suggest that combustor wall cooling needs to be optimized from the point of view of structural integrity and thermodynamic irreversibility.

Chitosan nanoparticles mitigate Alternaria leaf spot disease of chilli in nitric oxide dependent way.

The present study focuses on protection of emerging Alternaria leaf spot disease of chilli by application of chitosan nanoparticles (CNP). CNP was prepared by ionotropic gelation method and characterized. Antifungal potential of CNP was also checked against Alternaria alternata and its mechanisms were unraveled. Foliar application of CNP (0.001%) improved plant innate immunity in two chilli cultivars (one tolerant and one susceptible) by inducing the activities of different defense related enzymes along with total phenol and flavonoid. CNP application also induced callose deposition and reduced cell death in both the cultivar. Signaling molecule nitric oxide (NO) also augmented in CNP treated sets which were confirmed by both biochemical and microscopic data. In order to find out involvement of NO in CNP induced innate immunity in chilli cultivars, both NO surplus and NO depleted conditions were artificially created and defense responses were recorded. It was interesting to note that CNP mediated enhancement of defense responses in chilli plants was compromised in NO depleted condition. These results signify possible involvement of NO in CNP induced defense responses in chilli plants. It is evident from our results that CNP can be used to protect chilli plants against this fungal disease to develop a sustainable management strategy.

Chitosan/benzyloxy-benzaldehyde modified ZnO nano template having optimized and distinct antiviral potency to human cytomegalovirus.

Utilization of biomolecules encapsulated nano particles is currently originating ample attention to generate unconventional nanomedicines in antiviral research. Zinc oxide nanoparticle has been extensively studied for antimicrobial, antifungal and antifouling properties due to high surface to volume ratios and distinctive chemical as well as physical properties. Nevertheless, still minute information is available on their response on viruses. Here, in situ nanostructured and polysaccharide encapsulated ZnO NPs are fabricated with having antiviral potency and low cytotoxicity (%viability ~ 90%) by simply controlling the formation within interspatial 3D networks of hydrogels through perfect locking mechanism. The two composites ChH@ZnO and ChB@ZnO shows exceedingly effective antiviral activity toward Human cytomegalovirus (HCMV) having cell viability 93.6% and 92.4% up to 400 µg mL-1 concentration. This study brings significant insights regarding the role of ZnO NPs surface coatings on their nanotoxicity and antiviral action and could potentially guide to the development of better antiviral drug.

Mycochemical Profiling and Antioxidant Activity of Two Different Tea Preparations from Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes).

Mushrooms have become the new superfood with their many bioactive metabolites and are potential candidates in the field of herbal medicine. Since not all mushrooms can be consumed whole, their active constituents and therapeutic benefits can be had in the form of beverages specially teas or coffees. In the present study, two forms of teas, infusion and decoction, were prepared from Hericium erinaceus (Bull.) Pers., a very popular mushroom in Chinese medicine. Both forms of tea were studied mycochemically and medicinally and a comparative view was presented on the basis of the findings. The tea preparations were rich in bioactive mycochemicals; interestingly, the infusion contained a higher amount of phenol (1.72 mg gallic acid equivalent/g of dry weight of mushrooms) than decoction (0.28 mg gallic acid equivalent/g of dry weight of mushrooms). Lycopene and ß-carotene were found in very minute amounts. Both infusion and decoction exhibited good free radical scavenging potential, reducing power, and total antioxidant properties. However, the infusion fraction produced overall better results than the decoction fraction. Finally, the results suggest that H. erinaceus is a potent source of natural antioxidant and also can be consumed as a beverage.

Modulation of immune response in Ebola virus disease.

Ebola virus disease targets and destroys immune cells, including macrophages and dendritic cells, leading to impairment of host response. After infection, a combination of strategies including alteration and evasion of immune response culminating in a strong inflammatory response can lead to multi-organ failure and death in most infected patients. This review discusses immune response dynamics, mainly focusing on how Ebola manipulates innate and adaptive immune responses and strategizes to thwart host immune responses. We also discuss the challenges and prospects of developing therapeutics and vaccines against Ebola.

Structure and dynamics of small-scale turbulence in vaporizing two-phase flows.

Improving our fundamental understanding of multiphase turbulent flows will be beneficial for analyses of a wide range of industrial and geophysical processes. Herein, we investigate the topology of the local flow in vaporizing forced homogeneous isotropic turbulent two-phase flows. The invariants of the velocity-gradient, rate-of-strain, rate-of-rotation tensors, and scalar gradient were computed and conditioned for different distances from the liquid-gas surface. A Schur decomposition of the velocity gradient tensor into a normal and non-normal parts was undertaken to supplement the classical double decomposition into rotation and strain tensors. Using direct numerical simulations results, we show that the joint probability density functions of the second and third invariants have classical shapes in all carrier-gas regions but gradually change as they approach the carrier-liquid interface. Near the carrier-liquid interface, the distributions of the invariants are remarkably similar to those found in the viscous sublayer of turbulent wall-bounded flows. Furthermore, the alignment of both vorticity and scalar gradient with the strain-rate field changes spatially such that its universal behaviour occurs far from the liquid-gas interface. We found also that the non-normal effects of the velocity gradient tensor play a crucial role in explaining the preferred alignment.

Prospecting medicinal properties of Lion's mane mushroom.

Hericium erinaceus (Bull.) Persoon, a popular medicinal edible mushroom, owns a long history of usage in traditional Chinese medicine and also in other oriental countries. Along with this, its several bioactive compounds have been evolved into food supplements. Meanwhile, this present investigation aimed at extracting bioactive components from fruiting bodies of H. erinaceus using two different solvents and evaluating its in vitro antioxidant, antimicrobial, and antiproliferative efficacy. Chemical analysis showed extracts were rich in phenol, flavonoids, and ascorbic acids while lesser amount of carotenoids were also detected in these extracts. Both extracts were able to scavenge 1,1-diphenyl-2-picrylhydrazyl (~76%) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) radicals (~81%) and also showed chelating activity (~73.05%). The ethanolic extract exhibited the highest antioxidant activity (total antioxidant capacity 2.17 µg ascorbic acid equivalent/mg of extract) whereas methanolic extract showed moderate capacity (total antioxidant capacity 1.42 µg ascorbic acid equivalent/mg of extract). All extracts displayed antibacterial activity against both Gram-positive and Gram-negative bacteria as well (minimum inhibition concentration 1,575-2,750 µg/ml) although methanolic extract showed some selectivity towards bacterial strains. Apart from these, ethanolic fraction has found to exhibit potent cytotoxicity (IC50 403.12 µg/ml) towards lung adenocarcinoma cells. These studies thus provide the reference data that could support this mushroom as an easily accessible source of natural bioactive components. PRACTICAL APPLICATIONS: Mushroom extracts have long been traditionally used as miracle medicine to treat an extensive range of ailments. These findings indicate the potential benefits of the Hericium erinaceus (Bull.) Persoon extracts for the development of multi-target therapeutics as well as extraction with appropriate solvents also provide leads for the isolation of various principle compounds. The extracts thus could be used to treat oxidative stress-related disorders as they are found to contain antioxidant compounds like phenols and others and also they possessed good antimicrobial and anticancer activity.