Epigenetic reprogramming of T cells: unlocking new avenues for cancer immunotherapy.

T cells, a key component of cancer immunotherapy, undergo a variety of histone modifications and DNA methylation changes since their bone marrow progenitor stages before developing into CD8+ and CD4+ T cells. These T cell types can be categorized into distinct subtypes based on their functionality and properties, such as cytotoxic T cells (Tc), helper T cells (Th), and regulatory T cells (Treg) as subtypes for CD8+ and CD4+ T cells. Among these, the CD4+ CD25+ Tregs potentially contribute to cancer development and progression by lowering T effector (Teff) cell activity under the influence of the tumor microenvironment (TME). This contributes to the development of therapeutic resistance in patients with cancer. Subsequently, these individuals become resistant to monoclonal antibody therapy as well as clinically established immunotherapies. In this review, we delineate the different epigenetic mechanisms in cancer immune response and its involvement in therapeutic resistance. Furthermore, the possibility of epi-immunotherapeutic methods based on histone deacetylase inhibitors and histone methyltransferase inhibitors are under investigation. In this review we highlight EZH2 as the principal driver of cancer cell immunoediting and an immune escape regulator. We have addressed in detail how understanding T cell epigenetic regulation might bring unique inventive strategies to overcome drug resistance and increase the efficacy of cancer immunotherapy.

ZMYND8 Is a Regulator of Sonic Hedgehog Signaling in ATRA-Mediated Differentiation of Neuroblastoma Cells.

Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8) is a crucial epigenetic regulator that plays a multifaceted role in governing a spectrum of vital cellular processes, encompassing proliferation, apoptosis, migration, tumor suppression, and differentiation. It has emerged as a key player in neuronal differentiation by orchestrating the expression of neuronal lineage-committed genes. The present study uncovers the role of ZMYND8 in regulating the Sonic Hedgehog (SHH) signaling axis, which is crucial for neuronal differentiation. Genetic deletion of ZMYND8 leads to a significant reduction in SHH pathway genes, GLI1, and PTCH1 expression during all-trans-retinoic acid (ATRA)-induced differentiation. ZMYND8 and RNA pol II S5P are found to co-occupy the GLI1 and PTCH1 gene promoters, positively impacting their gene transcription upon ATRA treatment. Interestingly, ZMYND8 is found to counteract the inhibitory effects of Cyclopamine that block the upstream SHH pathway protein SMO, resulting in enhanced neurite formation in neuroblastoma cells following their treatment with ATRA. These results indicate that ZMYND8 is an epigenetic regulator of the SHH signaling pathway and has tremendous therapeutic potential in ATRA-mediated differentiation of neuroblastoma.

Fatty acid oxidation fuels agonist-induced platelet activation and thrombus formation: Targeting ß-oxidation of fatty acids as an effective anti-platelet strategy.

Platelet mitochondria possess remarkable plasticity for oxidation of energy substrates, where metabolic dependency on glucose or fatty acids is higher than glutamine. Since platelets metabolize nearly the entire pool of glucose to lactate rather than fluxing through mitochondrial tricarboxylic acid cycle, we posit that majority of mitochondrial ATP, which is essential for platelet granule secretion and thrombus formation, is sourced from oxidation of fatty acids. We performed a comprehensive analysis of bioenergetics and function of stimulated platelets in the presence of etomoxir, trimetazidine and oxfenicine, three pharmacologically distinct inhibitors of ß-oxidation. Each of them significantly impaired oxidative phosphorylation in unstimulated as well as thrombin-stimulated platelets leading to a small but consistent drop in ATP level in activated cells due to a lack of compensation from glycolytic ATP. Trimetazidine and oxfenicine attenuated platelet aggregation, P-selectin externalization and integrin αIIb ß3 activation. Both etomoxir and trimetazidine impeded agonist-induced dense granule release and platelet thrombus formation on collagen under arterial shear. The effect of inhibitors on platelet aggregation and dense granule release was dose- and incubation time- dependent with significant inhibition at higher doses and prolonged incubation times. Neither of the inhibitors could protect mice from collagen-epinephrine-induced pulmonary embolism or prolong mouse tail bleeding times. However, mice pre-administered with etomoxir, trimetazidine and oxfenicine were protected from ferric chloride-induced mesenteric thrombosis. In conclusion, ß-oxidation of fatty acids sustains ATP level in stimulated platelets and is therefore essential for energy-intensive agonist-induced platelet responses. Thus, fatty acid oxidation may constitute an attractive therapeutic target for novel antiplatelet agents.

One-Pot Tandem Aldol-Cycloetherification Protocol in the Enantioselective Synthesis of Davanoids.

Total synthesis of cis and trans diastereomers of prenylated davanoids like davanone, nordavanone, and davana acid ethyl ester was achieved in an enantioselective strategy. Various other davanoids could also be synthesized using standard procedures from the Weinreb amides derived from davana acids. Enantioselectivity in our synthesis was achieved employing a Crimmins' non-Evans syn aldol reaction that fixed the stereochemistry of the C3-hydroxyl group, while the C2-methyl group was epimerized in a late stage of the synthesis. A Lewis acid-mediated cycloetherification reaction was used to establish the tetrahydrofuran core of these molecules. Interestingly, a slight alteration of the Crimmins' non-Evans syn aldol protocol led to the complete conversion of the aldol adduct to the core tetrahydrofuran ring of davanoids, thus essentially dovetailing two important steps in the synthesis. The resulting one-pot tandem aldol-cycloetherification strategy enabled the enantioselective synthesis of trans davana acid ethyl esters and 2-epi-davanone/nordavanone in just three steps in excellent overall yields. The modularity of the approach will enable the synthesis of various other isomers in stereochemically pure forms for further biological profiling of this important class of molecules.

Current Scenario and Future Prospects of Endophytic Microbes: Promising Candidates for Abiotic and Biotic Stress Management for Agricultural and Environmental Sustainability.

Globally, substantial research into endophytic microbes is being conducted to increase agricultural and environmental sustainability. Endophytic microbes such as bacteria, actinomycetes, and fungi inhabit ubiquitously within the tissues of all plant species without causing any harm or disease. Endophytes form symbiotic relationships with diverse plant species and can regulate numerous host functions, including resistance to abiotic and biotic stresses, growth and development, and stimulating immune systems. Moreover, plant endophytes play a dominant role in nutrient cycling, biodegradation, and bioremediation, and are widely used in many industries. Endophytes have a stronger predisposition for enhancing mineral and metal solubility by cells through the secretion of organic acids with low molecular weight and metal-specific ligands (such as siderophores) that alter soil pH and boost binding activity. Finally, endophytes synthesize various bioactive compounds with high competence that are promising candidates for new drugs, antibiotics, and medicines. Bioprospecting of endophytic novel secondary metabolites has given momentum to sustainable agriculture for combating environmental stresses. Biotechnological interventions with the aid of endophytes played a pivotal role in crop improvement to mitigate biotic and abiotic stress conditions like drought, salinity, xenobiotic compounds, and heavy metals. Identification of putative genes from endophytes conferring resistance and tolerance to crop diseases, apart from those involved in the accumulation and degradation of contaminants, could open new avenues in agricultural research and development. Furthermore, a detailed molecular and biochemical understanding of endophyte entry and colonization strategy in the host would better help in manipulating crop productivity under changing climatic conditions. Therefore, the present review highlights current research trends based on the SCOPUS database, potential biotechnological interventions of endophytic microorganisms in combating environmental stresses influencing crop productivity, future opportunities of endophytes in improving plant stress tolerance, and their contribution to sustainable remediation of hazardous environmental contaminants.

An attempt to construct an indole-fused azabicyclo[3.3.1]nonane framework via radical cyclization.

The structural motif of an indole-fused azabicyclo[3.3.1]nonane is common in many biologically significant indole-based natural products. Because of its structural complexity, this N-bridged scaffold has become an enticing target for organic chemists. Many efficient strategies have been developed to access this ring system synthetically, but a radical approach remains unexplored. Herein, we report a radical-based strategy to construct an indole-fused azabicyclo[3.3.1]nonane structural framework. Although our initial attempt to use a Cp2TiCl-mediated radical cyclization method was found to be unsuccessful, an alternative approach using a SmI2-mediated radical cyclization protocol was effective for enabling the desired ring closure, leading to the target indole-fused azabicyclo[3.3.1]nonane ring system. The modular approach developed here can be extended with appropriate functionalities on this indole-fused N-bridged ring system to synthesize many alkaloids.

Visible-light-induced organophotocatalytic and singlet oxygen-initiated domino construction of 1,4-dihydropyridines, C-3 functionalized spiro[indoline-3,4'-pyridines] and C-11 functionalized spiro[indeno-[1,2-b]quinoxaline-11,4'-pyridines].

A highly efficient pot, atom, and step economical method for the construction of pharmacologically potent structurally functionalized 1,4-dihydropyridines, quaternary centered C-3 functionalized spiro[indoline-3,4'-pyridines], and C-11 functionalized spiro[indeno[1,2-b]quinoxaline-11,4'-pyridines] via rose bengal photoredox catalysis under blue LED irradiation in an aqueous medium at room temperature has been developed. The products were isolated in excellent yields within a short reaction time for a variety of functional groups under transition metal- and ligand-free energy-efficient conditions in a green solvent system with high reaction mass efficiency and process mass intensity, which are the key advantages of the current work.

Role of the Histone Acetyl Transferase MOF and the Histone Deacetylase Sirtuins in Regulation of H4K16ac During DNA Damage Repair and Metabolic Programming: Implications in Cancer and Aging.

The accurate repair of genomic damage mediated by ionizing radiation (IR), chemo- or radiomimetic drugs, or other exogenous agents, is necessary for maintenance of genome integrity, preservation of cellular viability and prevention of oncogenic transformation. Eukaryotes have conserved mechanisms designed to perceive and repair the damaged DNA quite efficiently. Among the different types of DNA damage, double strand breaks (DSB) are the most detrimental. The cellular DNA DSB response is a hierarchical signaling network that integrates damage sensing and repair with chromatin structural changes that involve a range of pre-existing and induced covalent modifications. Recent studies have revealed that pre-existing histone modifications are important contributors within this signaling/repair network. This chapter discusses the role of a critical histone acetyl transferase (HAT) known as MOF (males absent on the first) and the histone deacetylases (HDACs) Sirtuins on histone H4K16 acetylation (H4K16ac) and DNA damage repair. We also discuss the role of this important histone modification in light of metabolic rewiring and its role in regulating human pathophysiologic states.

Microalgal Carotenoids: Therapeutic Application and Latest Approaches to Enhance the Production.

Microalgae are microscopic photosynthetic organisms frequently found in fresh and marine water ecosystems. Various microalgal species have been considered a reservoir of diverse health-value products, including vitamins, proteins, lipids, and polysaccharides, and are broadly utilized as food and for the treatment of human ailments such as cancer, cardiovascular diseases, allergies, and immunodeficiency. Microalgae-derived carotenoids are the type of accessory pigment that possess light-absorbing potential and play a significant role in metabolic functions. To date, nearly a thousand carotenoids have been reported, but a very less number of microalgae have been used for the commercial production of carotenoids. This review article briefly discussed the carotenoids of microalgal origin and their therapeutic application. In addition, we have briefly compiled the optimization of culture parameters used to enhance microalgal carotenoid production. In addition, the latest biotechnological approaches used to improve the yields of carotenoid has also been discussed.

Nano-biochar: A novel solution for sustainable agriculture and environmental remediation.

Currently, the applications of biochar (BC) in agricultural practices and for environmental remediation purposes have demonstrated multifaceted advantages despite a few limitations. Nano-BC offers considerable opportunities especially for the remediation of hazardous contaminants as well as the improvement of crop productivity. Positive outcomes of nano-BC on soil physico-chemical and biological characteristics have indicated its suitability for agricultural applications. Nano-BC may effectively regulate the mobilization and sorption of important micro- and macro-nutrients, along with the hazardous contaminants including potentially toxic metals, pesticides, etc. Additionally, the sorption characteristics of nano-BC depends substantially on feedstock materials and pyrolysis temperatures. Nevertheless, the conducted investigations regarding nano-BC are in infant stages, requiring extensive field investigations. The nano-enhanced properties of BC on one hand dramatically improve its effectiveness and sustainability, on the other hand, there may be associated with toxicity development in diverse aquatic and/or terrestrial environments. Therefore, risk assessment on soil organisms and its indirect impact on human health is another area of concern linked with the field application of nano-BC. The present review delineates the potentiality of nano-BC as an emerging sorbent for sustainable agriculture and environmental applications.

Co-encapsulation of Pimpinella anisum and Coriandrum sativum essential oils based synergistic formulation through binary mixture: Physico-chemical characterization, appraisal of antifungal mechanism of action, and application as natural food preservative.

The present study aimed to co-encapsulate binary synergistic formulation of Pimpinella anisum and Coriandrum sativum (PC) essential oils (0.75:0.25) into chitosan nanoemulsion (Nm-PC) with effective inhibition against fungal proliferation, aflatoxin B1 (AFB1) secretion, and lipid peroxidation in stored rice. Physico-chemical characterization of Nm-PC by SEM, FTIR, and XRD confirmed successful encompassment of PC inside the chitosan nanomatrix with efficient interaction by functional groups and reduction in crystallinity. Nm-PC showed superior antifungal, antiaflatoxigenic, and antioxidant activities over unencapsulated PC. Reduction in ergosterol biosynthesis and enhanced leakage of Ca2+, K+, Mg2+ ions and 260, 280 nm absorbing materials by Nm-PC fumigation confirmed irreversible damage of plasma membrane in toxigenic Aspergillus flavus cells. Significant diminution of methylglyoxal in A. flavus cells by Nm-PC fumigation illustrated biochemical mechanism for antiaflatoxigenic activity, suggesting future exploitation for development of aflatoxin resistant rice varieties through green transgenic technology. In silico findings indicated specific stereo-spatial interaction of anethole and linalool with Nor-1 protein, validating molecular mechanism for AFB1 inhibition. In addition, in situ investigation revealed effective protection of stored rice against fungal occurrence, AFB1 biosynthesis, and lipid peroxidation without affecting organoleptic attributes. Moreover, mammalian non-toxicity of chitosan entrapped PC synergistic nanoformulation could provide exciting potential for application as eco-smart safe nano-green food preservative.

Insights into the Biosynthesis of Nanoparticles by the Genus Shewanella.

The exploitation of microorganisms for the fabrication of nanoparticles (NPs) has garnered considerable research interest globally. The microbiological transformation of metals and metal salts into respective NPs can be achieved under environmentally benign conditions, offering a more sustainable alternative to chemical synthesis methods. Species of the metal-reducing bacterial genus Shewanella are able to couple the oxidation of various electron donors, including lactate, pyruvate, and hydrogen, to the reduction of a wide range of metal species, resulting in biomineralization of a multitude of metal NPs. Single-metal-based NPs as well as composite materials with properties equivalent or even superior to physically and chemically produced NPs have been synthesized by a number of Shewanella species. A mechanistic understanding of electron transfer-mediated bioreduction of metals into respective NPs by Shewanella is crucial in maximizing NP yields and directing the synthesis to produce fine-tuned NPs with tailored properties. In addition, thorough investigations into the influence of process parameters controlling the biosynthesis is another focal point for optimizing the process of NP generation. Synthesis of metal-based NPs using Shewanella species offers a low-cost, eco-friendly alternative to current physiochemical methods. This article aims to shed light on the contribution of Shewanella as a model organism in the biosynthesis of a variety of NPs and critically reviews the current state of knowledge on factors controlling their synthesis, characterization, potential applications in different sectors, and future prospects.

Fabrication, characterization and practical efficacy of Myristica fragrans essential oil nanoemulsion delivery system against postharvest biodeterioration.

The present study deals with encapsulation of Myristica fragrans essential oil (MFEO) into chitosan nano-matrix, their characterization and assessment of antimicrobial activity, aflatoxin inhibitory potential, safety profiling and in situ efficacy in stored rice as environment friendly effective preservative to control the postharvest losses of food commodities under storage. Surface morphology of MFEO-chitosan nanoemulsion as well as encapsulation of MFEO was confirmed through SEM, FTIR and XRD analysis. In vitro release characteristics with biphasic burst explained controlled volatilization from nanoencapsulated MFEO. Unencapsulated MFEO exhibited fungitoxicity against 15 food borne molds and inhibited aflatoxin B1 secretion by toxigenic Aspergillus flavus LHP R14 strain. In contrast, nanoencapsulated MFEO showed better fungitoxicity and inhibitory effect on aflatoxin biosynthesis at lower doses. In situ efficacy of unencapsulated and nanoencapsulated MFEO on stored rice seeds exhibited effective protection against fungal infestation, aflatoxin B1 contamination, and lipid peroxidation. Both the unencapsulated and nanoencapsulated MFEO did not affect the germination of stored rice seeds confirming non-phytotoxic nature. In addition, negligible mammalian toxicity of unencapsulated MFEO (LD50 = 14,289.32 µL/kg body weight) and MFEO loaded chitosan nanoemulsion (LD50 = 9231.89 µL/kg body weight) as revealed through favorable safety profile recommend the industrial significance of nanoencapsulated MFEO as an effective green alternative to environmentally hazardous synthetic pesticides for protection of food commodities during storage.

Measurement of legacy and emerging flame retardants in indoor dust from a rural village (Kopawa) in Nepal: Implication for source apportionment and health risk assessment.

Under the Stockholm Convention, signatory countries are obliged to direct source inventories, find current sources, and provide ecological monitoring evidence to guarantee that the encompassing levels of persistent organic pollutants (POPs) are declining. However, such monitoring of different types of POPs are to a great degree constrained in most developing countries including Nepal and are primarily confined to suspected source area/ densely populated regions. In this study, 9 polybrominated diphenyl ethers (PBDEs), 2 dechlorane plus (DPs), 6 novel brominated flame retardants (NBFRs) and 8 organophosphate ester flame retardants (OPFRs) were investigated in indoor dust from a rural area (Kopawa) in Nepal in order to evaluate their occurrence/level, profile, spatial distribution and their sources. Additionally, health risk exposure was estimated to anticipate the possible health risk to the local population. The results showed that OPFRs was the most abundant FR measured in the dust. The concentration of ∑8OPFRs was about 2, 3 and 4 orders of magnitude higher than the ∑6NBFRs, ∑9PBDEs, and ∑2DPs, respectively. Tris (methylphenyl) phosphate (TMPP) and Tris (2-ethylhexyl) phosphate (TEHP) were the most abundant OPFRs analyzed in the dust; while decabromodiphenyl ethane (DBDPE) exceeded among NBFRs. Likewise, 2,2',3,3',4,4',5,5',6,6'-decabromodiphenylether (BDE-209) was the most identified chemical among PBDEs. The total organic carbon (TOC) content in dust was significantly and positively connected with octa-BDEs (Rho = 0.615, p < 0.01), BTBPE (Rho = 0.733, p < 0.01), TPHP (Rho = 0.621, p < 0.01), TEHP (Rho = 0.560, p < 0.01) and TMPPs (Rho = 0.550, p < 0.01), while black carbon (BC) was either weakly related or not related, suggesting little or no impact of BC in the distribution of FRs. Principal component analysis indicated the contribution from commercial penta-, octa- and deca-BDEs formulation, the adhesive substance, food packaging and paints, and degradation of BDE-209 as the essential sources of FRs. Health risk exposure estimates showed that dermal absorption via dust as the primary route of FRs intake. The estimated daily exposure of PBDEs, NBFRs and OPFRs were 2-10 orders of magnitude lower than their corresponding reference dose (RfD), suggesting insignificant risk. However, other routes such as inhalation and dietary intake might still be significant in the case of Kopawa which should be tested in future.

Antimicrobial activity, antiaflatoxigenic potential and in situ efficacy of novel formulation comprising of Apium graveolens essential oil and its major component.

The present study reports the formulation of Apium graveolens essential oil (AGEO) with its major components linalyl acetate (LA) and geranyl acetate (GA) (1:1:1) as a novel green preservative for protection of postharvest food commodities from fungal infestations, aflatoxin B1 (AFB1) secretion, free radical generation and lipid peroxidation. The essential oil based novel formulation displayed considerable inhibitory action against fourteen food borne molds responsible for deterioration of stored food commodities, in addition to the most toxigenic strain of Aspergillus flavus (AFLHPR14) isolated from fungal and aflatoxin contaminated rice seeds. The observed higher efficacy of designed formulation was due to the synergistic action of essential oil and its major components. Fungal plasma membrane was recorded as the possible target site of antifungal action of the formulation as revealed through reduction in membrane ergosterol content, increased intracellular propidium iodide (PI) fluorescence and enhanced leakage of cellular ions (sodium, potassium, calcium) and 260, 280 nm absorbing materials. Further, inhibition of methylglyoxal (an aflatoxin inducer) confirmed the aflatoxin inhibitory potential of novel formulation based on essential oil and its major components. High antioxidant potential as observed through DPPH and ABTS·+ radical scavenging assay, improved phenolic content, considerable inhibition of lipid peroxidation in stored rice seeds, in situ efficacy on AFB1 inhibition in food system under storage container system, acceptable sensorial characteristics and favorable safety profile during animal trials suggest the recommendation of the designed formulation for large scale application as green preservative by food and agriculture based industries against fungal and aflatoxin contamination of stored commodities.

Reconstructing the demographic history of the Himalayan and adjoining populations.

The rugged topography of the Himalayan region has hindered large-scale human migrations, population admixture and assimilation. Such complexity in geographical structure might have facilitated the existence of several small isolated communities in this region. We have genotyped about 850,000 autosomal markers among 35 individuals belonging to the four major populations inhabiting the Himalaya and adjoining regions. In addition, we have genotyped 794 individuals belonging to 16 ethnic groups from the same region, for uniparental (mitochondrial and Y chromosomal DNA) markers. Our results in the light of various statistical analyses suggest a closer link of the Himalayan and adjoining populations to East Asia than their immediate geographical neighbours in South Asia. Allele frequency-based analyses likely support the existence of a specific ancestry component in the Himalayan and adjoining populations. The admixture time estimate suggests a recent westward migration of populations living to the East of the Himalaya. Furthermore, the uniparental marker analysis among the Himalayan and adjoining populations reveal the presence of East, Southeast and South Asian genetic signatures. Interestingly, we observed an antagonistic association of Y chromosomal haplogroups O3 and D clines with the longitudinal distance. Thus, we summarise that studying the Himalayan and adjoining populations is essential for a comprehensive reconstruction of the human evolutionary and ethnolinguistic history of eastern Eurasia.

MBL2 variations and malaria susceptibility in Indian populations.

Human mannose-binding lectin (MBL) encoded by the MBL2 gene is a pattern recognition protein and has been associated with many infectious diseases, including malaria. We sought to investigate the contribution of functional MBL2 gene variations to Plasmodium falciparum malaria in well-defined cases and in matched controls. We resequenced the 8.7 kb of the entire MBL2 gene in 434 individuals clinically classified with malaria from regions of India where malaria is endemic. The study cohort included 176 patients with severe malaria, 101 patients with mild malaria, and 157 ethnically matched asymptomatic individuals. In addition, 830 individuals from 32 socially, linguistically, and geographically diverse endogamous populations of India were investigated for the distribution of functional MBL2 variants. The MBL2 -221C (X) allelic variant is associated with increased risk of malaria (mild malaria odds ratio [OR] = 1.9, corrected P value [P(Corr)] = 0.0036; severe malaria OR = 1.6, P(Corr) = 0.02). The exon1 variants MBL2*B (severe malaria OR = 2.1, P(Corr) = 0.036; mild versus severe malaria OR = 2.5, P(Corr) = 0.039) and MBL2*C (mild versus severe malaria OR = 5.4, P(Corr) = 0.045) increased the odds of having malaria. The exon1 MBL2*D/*B/*C variant increased the risk for severe malaria (OR = 3.4, P(Corr) = 0.000045). The frequencies of low MBL haplotypes were significantly higher in severe malaria (14.2%) compared to mild malaria (7.9%) and asymptomatic (3.8%). The MBL2*LYPA haplotypes confer protection, whereas MBL2*LXPA increases the malaria risk. Our findings in Indian populations demonstrate that MBL2 functional variants are strongly associated with malaria and infection severity.

Revealing the seed microbiome: Navigating sequencing tools, microbial assembly, and functions to amplify plant fitness.

Microbial communities within seeds play a vital role in transmitting themselves to the next generation of plants. These microorganisms significantly impact seed vigor and early seedling growth, for successful crop establishment. Previous studies reported on seed-associated microbial communities and their influence on processes like dormancy release, germination, and disease protection. Modern sequencing and conventional methods reveal microbial community structures and environmental impacts, these information helps in microbial selection and manipulation. These studies form the foundation for using seed microbiomes to enhance crop resilience and productivity. While existing research has primarily focused on characterizing microbiota in dried mature seeds, a significant gap exists in understanding how these microbial communities assemble during seed development. The review also discusses applying seed-associated microorganisms to improve crops in the context of climate change. However, limited knowledge is available about the microbial assembly pattern on seeds, and their impact on plant growth. The review provides insight into microbial composition, functions, and significance for plant health, particularly regarding growth promotion and pest control.

UBR7 E3 Ligase Suppresses Interferon-ß Mediated Immune Signaling by Targeting Sp110 in Hepatitis B Virus-Induced Hepatocellular Carcinoma.

A newly discovered E3 ubiquitin ligase, UBR7, plays a crucial role in histone H2BK120 monoubiquitination. Here, we report a novel function of UBR7 in promoting hepatitis B virus (HBV) pathogenesis, which further leads to HBV-induced hepatocellular carcinoma (HCC). Transcriptomics analysis from HCC patients revealed the deregulation of UBR7 in cancer. Remarkably, targeting UBR7, particularly its catalytic function, led to a significant decrease in viral copy numbers. We also identified the speckled family protein Sp110 as an important substrate of UBR7. Notably, Sp110 has been previously shown to be a resident of promyelocytic leukemia nuclear bodies (PML-NBs), where it remains SUMOylated, and during HBV infection, it undergoes deSUMOylation and exits the PML body. We observed that UBR7 ubiquitinates Sp110 at critical residues within its SAND domain. Sp110 ubiquitination downregulates genes in the type I interferon response pathway. Comparative analysis of RNA-Seq from the UBR7/Sp110 knockdown data set confirmed that the IFN-ß signaling pathway gets deregulated in HCC cells in the presence of HBV. Single-cell RNA-Seq analysis of patient samples further confirmed the inverse correlation between the expression of Sp110/UBR7 and the inflammation score. Notably, silencing of UBR7 induces IRF7 phosphorylation, thereby augmenting interferon (IFN)-ß and the downstream interferon-stimulated genes (ISGs). Further, wild-type but not the ubiquitination-defective mutant of Sp110 could be recruited to the type I interferon response pathway genes. Our study establishes a new function of UBR7 in non-histone protein ubiquitination, promoting viral persistence, and has important implications for the development of therapeutic strategies targeting HBV-induced HCC.

An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant.

BACKGROUND: The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anti-cancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature. OBJECTIVE: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research. METHODS: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, Sci-Finder, other online journals and books for detailed analysis. RESULTS: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare. CONCLUSION: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.