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Abstract—Lactate dehydrogenase (LDH) is a terminating enzyme in the metabolic pathway of anaerobic glycolysis with end product of lactate from glucose. The lactate formation is crucial in the metabolism of glucose when oxygen is in inadequate supply. Lactate can also be formed and utilised by different cell types under fully aerobic conditions. Blood LDH is the marker enzyme, which predicts mortality in many conditions such as ARDS, serious COVID-19 and cancer patients. Lactate plays a critical role in normal physiology of humans including an energy source, a signaling molecule and a pH regulator. Depending on the pH, lactate exists as the protonated acidic form (lactic acid) at low pH or as sodium salt (sodium lactate) at basic pH. Lactate can affect the immune system and act as a signaling molecule, which can provide a “danger” signal for life. Several reports provide evidence that the serum lactate represents a chemical marker of severity of disease similar to LDH under inflammatory conditions. Since the mortality rate is much higher among COVID-19 patients, associated with high serum LDH, this article is aimed to review the LDH as a therapeutic target and lactate as potential marker for monitoring treatment response of inflammatory diseases. Finally, the review summarises various LDH inhibitors, which offer potential applications as therapeutic agents for inflammatory diseases, associated with high blood LDH. Both blood LDH and blood lactate are suggested as risk factors for the mortality of patients in serious inflammatory diseases.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a virus called “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).” In the majority of patients, infection with COVID-19 may be asymptomatic or may cause only mild symptoms. However, in some patients, there can also be immunological problems, such as macrophage activation syndrome (CSS) that results in cytokine storm syndrome (CSS) and acute respiratory distress syndrome (ARDS). Comprehension of host-microbe communications is the critical aspect in the advancement of new therapeutics against infectious illnesses. Endogenous animal lectins, a class of proteins, may perceive non-self glycans found on microorganisms. Serum mannose-binding lectin (sMBL), as a part of the innate immune framework, recognizes a wide range of microbial microorganisms and activates complement cascade via an antibody-independent pathway. Although the molecular basis for the intensity of SARS-CoV-2 infection is not generally understood, scientific literature indicates that COVID-19 is correlated with unregulated activation of the complement in terms of disease severity. Disseminated intravascular coagulation (DIC), inflammation, and immune paralysis contribute to unregulated complement activation. Pre-existing genetic defects in MBL and their association with complement play a major role in immune response dysregulation caused by SARS-CoV-2. In order to generate anti-complement-based therapies in Covid-19, an understanding of sMBL in immune response to SARS-CoV-2 and complement is therefore essential. This review highlights the role of endogenous sMBL and complement activation during SARS-CoV-2 infection and their therapeutic management by various agents, mainly plant lectins, since antiviral mannose-binding plant lectins (pMBLs) offer potential applications in the prevention and control of viral infections.

Glycosylated nanoparticles (NPs) have drawn a lot of attention in the biomedical field over the past few decades, particularly in applications like targeted drug delivery. Mannosylated NPs and mannan-binding lectins/proteins (MBL/MBP) are emerging as promising tools for delivery of drugs, medicines, and enzymes to targeted tissues and cells as nanocarriers, enhancing their therapeutic benefits while avoiding the adverse effects of the drug. The occurrence of plenty of lectin receptors and their mannan ligands on cell surfaces makes them multifaceted carriers appropriate for specific delivery of bioactive drug materials to their targeted sites. Thus, the present review describes the tethering of mannose (Man) to several nanostructures, like micelles, liposomes, and other NPs, applicable for drug delivery systems. Bioadhesion through MBL-like receptors on cells has involvements applicable to additional arenas of science, for example gene delivery, tissue engineering, biomaterials, and nanotechnology. This review also focuses on the role of various aspects of drug/antigen delivery using (i) mannosylated NPs, (ii) mannosylated lectins, (iii) amphiphilic glycopolymer NPs, and (iv) natural mannan-containing polysaccharides, with most significant applications of MBL-based NPs as multivalent scaffolds, using different strategies.Mannosylated NPs and/or MBL/MBP are coming up as viable and versatile tools as nanocarriers to deliver drugs and enzymes precisely to their target tissues or cells. The presence of abundant number of lectin receptors and their mannan ligands on cell surfaces makes them versatile carriers suitable for the targeted delivery of bioactive drugs.

Quantification of nitrogen (N) transformation rates in tropical estuarine-coastal water coupled systems undergoing anthropogenic disturbances is scant. A thorough understanding of these metabolic rates is required to evolve a mitigation strategy to save such systems from further degradation. Here, we report the first measurements of ammonium (NH₄ ⁺) and nitrate (NO₃ ⁻) uptake along with N₂ fixation rates in the Cochin estuary, a tropical eutrophic ecosystem along the west coast of India, and two transects (off Cochin and off Mangalore) in the coastal Arabian Sea. In general, the Cochin estuary sustained higher uptake rates of NH₄ ⁺ (0.32–0.91 μmol N l⁻¹ h⁻¹) and NO₃ ⁻ (0.01–0.38 μmol N l⁻¹ h⁻¹) compared to coastal waters. The N uptake in the nearshore waters of Cochin transect (NH₄ ⁺ : 0.34 μmol N l⁻¹ h⁻¹ and NO₃ ⁻ : 0.18 μmol N l⁻¹ h⁻¹) was influenced more by estuarine discharge than was the Mangalore transect (NH₄ ⁺ : 0.02 μmol N l⁻¹ h⁻¹ and NO₃ ⁻ : 0.03 μmol N l⁻¹ h⁻¹). Despite high dissolved inorganic nitrogen (DIN) concentrations, the Cochin estuary also showed higher N₂ fixation rates (0.59–1.31 nmol N l⁻¹ h⁻¹) than the coastal waters (0.33–0.55 nmol N l⁻¹ h⁻¹). NH₄ ⁺ was the preferred substrate for phytoplankton growth, both in the Cochin estuary and coastal waters, indicating the significance of regenerative processes in primary production. A significant negative correlation between total nitrogen (TN): total phosphorus (TP), and NH₄ ⁺ uptake (as well as N₂ fixation) rates in the estuary suggests that nutrient stoichiometry plays a major role in modulating N transformation rates in the Cochin estuary.

The growing number of oxygen-deficient coastal zones around the world and their impacts on marine life has always been a controversial issue as their development is largely attributed to anthropogenic activities which can be mitigated by human actions. However, contrary to this prevailing understanding, we show here for the first time, using new coherent datasets from estuaries to coastal to offshore regions, that the world’s largest hypoxic-anoxic zone along the west coast of India is formed through a natural process, i.e. upwelling of deoxygenated waters during the summer monsoon. We further demonstrate that the persistence and extent of this coastal oxygen deficiency depend on the degree of deoxygenation of source waters for the upwelling. Consequently, the anoxia is confined only to the central shelf between 11° and 18° N, which is equivalent to almost half of the western Indian shelf, where upwelling brings suboxic waters from the core oxygen minimum zone in the Arabian Sea.

Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by a gradual decline in cognitive and memory functions of the aged peoples. Long-term exposure to heavy metals (aluminium and iron) cause neurotoxicity by amyloid plaques accumulation, tau phosphorylation, increased oxidative stress, neuroinflammation, and cholinergic neurons degeneration, contributes to the development of AD-like symptoms. The present research work is designed to investigate the neuroprotective effect of spermine in aluminium chloride (AlCl 3 ), and iron (Fe) induced AD-like symptoms in rats. Rats were administered of AlCl 3 (100 mg/kg p.o.) alone and in combination with iron (120 μg/g, p.o.) for 28 days. Spermine (5 and 10 mg/kg) through intraperitoneal (i.p.) route was given for 14 days. The recognition and spatial memory impairment were tasted using Morris water maze (MWM), actophotometer, and Novel Object Recognition test (NORT). All the rats were sacrificed on day 29, brains were isolated, and tissue homogenate was used for neuroinflammatory, biochemical, neurotransmitters, metals concentration, and nuclear factor-kappa B (NF-κB) analysis. In the present study, AlCl 3 and iron administration elevated oxidative stress, cytokines release, dysbalanced neurotransmitters concentration, and biochemical changes. Rats treated with spermine dose-dependently improved the recognition and spatial memory, attenuated proinflammatory cytokine release, and restored neurotransmitters concentration and antioxidant enzymes. Spermine also mitigated the increased beta-amyloid (Aβ42), with downregulation of tau phosphorylation. Furthermore, spermine augmented the hippocampal levels of B cell leukaemia/lymphoma-2 (Bcl-2), diminished nuclear factor-kappa B (NF-κB) and caspase-3 (casp-3) expression. Moreover, spermine exhibited the neuroprotective effect through anti-inflammatory, antioxidant, neurotransmitters restoration, anti-apoptotic Aβ42 concentration.

Osteopontin (OPN) promotes hepatic fibrosis, and developing therapies targeting OPN expression in settings of hepatic injury holds promise. The polyphenol epigallocatechin-3-gallate (EGCG), found in high concentrations in green tea, downregulates OPN expression through OPN mRNA degradation, but the mechanism is unknown. Previous work has shown that microRNAs can decrease OPN mRNA levels, and other studies have shown that EGCG modulates the expression of multiple microRNAs. In our study, we first demonstrated that OPN induces hepatic stellate cells to transform into an activated state. We then identified three microRNAs which target OPN mRNA: miR-181a, miR-10b, and miR-221. In vitro results show that EGCG upregulates all three microRNAs, and all three microRNAs are capable of down regulating OPN mRNA when administered alone. Interestingly, only miR-221 is necessary for EGCG-mediated OPN mRNA degradation and miR-221 inhibition reduces the effects of EGCG on cell function. In vivo experiments show that thioacetamide (TAA)-induced cell cytotoxicity upregulates OPN expression; treatment with EGCG blocks the effects of TAA. Furthermore, chronic treatment of EGCG in vivo upregulates all three microRNAs equally, suggesting that in more chronic treatment all three microRNAs are involved in modulating OPN expression. We conclude that in in vitro and in vivo models of TAA-induced hepatic fibrosis, EGCG inhibits OPN-dependent injury and fibrosis. EGCG works primarily by upregulating miR-221 to accelerate OPN degradation. EGCG may therefore have utility as a protective agent in settings of liver injury.

The upwelling phenomenon plays a vital role within marine ecosystems, transporting essential nutrients from the bottom to the surface and boosting biological productivity. However, the bacterial community structure in upwelling zones along the western coast of India (WCI) is understudied. This research systematically examines bacterial diversity across three seasons—pre-monsoon (PR), monsoon (MN), and post-monsoon (PM)—using next-generation sequencing. Our findings show distinct spatial patterns of bacterial communities in the Arabian Sea and demonstrate that ecological variations influence bacterial distribution in this dynamic environment. During MN, the bacterial community exhibited greater species diversity but lower overall abundance compared to PR and PM. Non-Metric MDS cluster analysis revealed a 78% similarity (at order level) between PR and PM, indicating that MN supports unique bacterial diversity. KEGG analysis showed significant seasonal variations in metabolic functions, with increased functional potential during MN. Additionally, Carbohydrate-Active enZymes (CAZymes) analysis revealed distinct seasonal profiles, among which the GH13 enzymes were the most prevalent glycoside hydrolases during MN, predominantly being sucrose phosphorylase and glucosidase, known for breaking down glucan deposits derived from phytoplankton. The CAZymes profiles supported taxonomic and KEGG pathway findings, reinforcing that microbial communities are seasonally distinct and functionally adapted to changing availability of nutrients.

The lesser known coastal upwelling in the North Eastern Arabian Sea (NEAS) during summer monsoon, its associated dynamics and forcing mechanisms is elucidated for the first time using basin scale monthly time-series in-situ and satellite data. The presence of cool upwelled waters along northwest coast of India from July to early October with an associated increase in productivity was evident in both data. The low level Findlater jet blows towards west coast of India with high wind magnitude (10–12 m/s) during summer monsoon generates strong Ekman transport (1416 kg/m/s) at offshore and Ekman pumping velocity (1.349 m/s) at coastal region initiates upwelling. It was identified that the currents and remote forcing also regulate upwelling along the region. Although upwelling seems to exist along the northwest coast, it was weaker (25.5 °C) compared to the southwest coast where the SST dropped to 24 °C. The upwelling was observed in the south during June as a surface process, while it was observed along the northwest coast of India by the end of August. Even though the onset of upwelling in the NEAS and South Eastern Arabian Sea (SEAS) had a lag of two months, the recession of upwelling happened during late and early September respectively. The cause for the lag in the onset and cessation of upwelling between SEAS and NEAS is attributed to the propagation of Kelvin waves and southwest monsoon winds. The study also reveals that temperature and chlorophyll profiles show bi-modal peaks of high and low associated with winter cooling (winter) and upwelling (summer).

Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment significantly influence cancer growth and metastasis. Transforming growth factor-β (TGF-β) is known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN−) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-β1 to mediate adoption of the CAF phenotype. This OPN–TGF-β1 pathway requires the transcription factor, myeloid zinc finger 1 (MZF1). In vivo studies with xenotransplant models in NOD-scid mice showed that OPN expression increases cancer growth and metastasis by mediating MSC-to-CAF transformation in a process that is MZF1 and TGF-β1 dependent. We conclude that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN–MZF1–TGF-β1 pathway.