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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.
•Parkinson’s disease is a multifactorial neurodegenerative disorder caused by various pathological insult led to dopaminergic neurons loss.•Excessive exposure to heavy metals and their accumulations ...in brain produce Parkinson’s disease like symptoms.•Heavy metals promote oxidative stress, mitochondrial dysfunction and formation of α-synuclein leads to dopaminergic neuronal damage.•Metal’s chelators and natural compounds are able to scavenge ROS, improve mitochondrial function and avert neuronal loss.
Parkinson's disease (PD) is a deliberately progressive neurological disorder, arises due to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of dopaminergic nerves and dopamine deficiency leads to motor symptoms characterized by rigidity, tremor, and bradykinesia. Heavy metals and trace elements play various physiological and pathological roles in the nervous system. Excessive exposure to toxic metals like mercury (Hg), lead (Pb), copper (Cu), zinc (Zn), iron (Fe), manganese (Mn), aluminium (Al), arsenic (As), cadmium(cd), and selenium (Se) cross the blood-brain barrier to enter into the brain and leads to dopaminergic neuronal degeneration. Excessive concentrations of heavy metals in the brain promote oxidative stress, mitochondrial dysfunction, and the formation of α-synuclein leads to dopaminergic neuronal damage. There is increasing evidence that heavy metals normally present in the human body in minute concentration also cause accumulation to initiate the free radical formation and affecting the basal ganglia signaling. In this review, we explored how these metals affect brain physiology and their roles in the accumulation of toxic proteins (α-synuclein and Lewy bodies). We have also discussed the metals associated with neurotoxic effects and their prevention as management of PD. Our goal is to increase the awareness of metals as players in the onset and progression of PD.
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.
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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.
ABSTRACT Observations of recurrent explosive events (EEs) with timescales of 3-5 minutes are reported. These EEs have been observed with the Interface Region Imaging Spectrograph (IRIS) and have a ...spatial dimension of along the slit. The spectral line profiles of C ii and Si iv become highly broadened both in red as well as blue wings. Several absorption lines on top of the broadened profiles were identified. In addition, emission lines corresponding to neutral lines such as Cl i 1351.66 , C i 1354.29 , and C i 1355.84 were identified. The C i 1354.29 and C i 1355.84 lines were found only during the EEs, whereas Cl i 1351.66 broadens during the EEs. The estimated lower limit on electron number density obtained using the line ratios of Si iv and O iv is about cm−3, suggesting that the observed events are most likely occurring at heights corresponding to a lower chromosphere. To the best of our knowledge, for the first time we have detected short-period variability (30 s and 60-90 s) within the EE bursts. Observations of the photospheric magnetic fields underneath EEs indicate that a negative polarity field emerges in the neighborhood of oppositely directed positive fields that undergo repetitive reconnection (magnetic flux cancellation) events. The dynamic changes observed in AIA 1700 , 1600 , C ii 1330 , and Si iv 1400 intensity images corresponded very well with the emergence and cancellation of photospheric magnetic field (negative polarity) on a timescale of 3-5 minutes. The observations reported here suggest that these EEs are formed due to magnetic reconnection and are occurring in the lower chromosphere.
Despite the omnipresence of microplastics (MPs), the studies around the western continental shelf of Indian Ocean (Eastern Arabian Sea-EAS) are uncovered and understudied. Thus, the present study was ...focused to understand the spatial distribution, characterization and risk assessment of MPs in sediment across seven coastal transects (10 to 50 m) all along the EAS shelf. The highest MPs concentration (MPs/kg d.w.) was detected in the northern EAS (NEAS; 2260 ± 1050) followed by central (CEAS; 1550 ± 1012) and southern (SEAS; 1300 ± 513) shelves. Among all distinct locations, the highest concentration of MPs (2500 ± 1042) was detected in the north coastal sediments off Mumbai, followed by off Mangalore (1480 ± 1169) in the center and off Kochi (1350 ± 212) in the south. MPs were found in the form of fibres, fragments and films with a predominance of fibres (~70-80 %). Approximately 74.6 % of the total MPs were in the size range of 300 μm to 5 mm. The surface of detected MPs was rough, irregular, and mechanical weathering features such as pits, grooves also observed and spotted with bacterial community structures. Polypropylene (PP; 34 %), polyisoprene (PIP; 19 %), butyl rubber (18 %), and low-density polyethylene (LDPE; 13 %) were dominant polymers. The pollution load index highlighted minor risk while the polymer hazard index exhibited a hazard level of V. Litter discharge, fishing activities, and active marine navigation are among the many high-risk sources of plastic contamination in this region. Due to the prevailing winds, currents, low sea surface height, and high precipitation, the conditions in the EAS are favorable for the accumulation of both sea-based and land-based particles. Hence, this study provides novel insights into the potential risks posed by MP to the IO rim and associated marine ecosystem which will enhance our knowledge of the ecological implications and consequences of MP pollution, ultimately aiding in developing effective management and mitigation strategies.
We investigate the off-limb active-region and quiet-Sun corona using spectroscopic data. The active region is clearly visible in several spectral lines formed in the temperature range of 1.1-2.8 MK. ...We derive the electron number density using the line ratio method, and the nonthermal velocity in the off-limb region up to the distance of 140 Mm. We compare density scale heights derived from several spectral line pairs with expected scale heights per the hydrostatic equilibrium model. Using several isolated and unblended spectral line profiles, we estimate nonthermal velocities in the active region and quiet Sun. Nonthermal velocities obtained from warm lines in the active region first show an increase and then later either a decrease or remain almost constant with height in the far off-limb region, whereas nonthermal velocities obtained from hot lines show consistent decrease. However, in the quiet-Sun region, nonthermal velocities obtained from various spectral lines show either a gradual decrease or remain almost constant with height. Using these obtained parameters, we further calculate Alfvén wave energy flux in both active and quiet-Sun regions. We find a significant decrease in wave energy fluxes with height, and hence provide evidence of Alfvén wave damping. Furthermore, we derive damping lengths of Alfvén waves in the both regions and find them to be in the range of 25-170 Mm. Different damping lengths obtained at different temperatures may be explained as either possible temperature-dependent damping or by measurements obtained in different coronal structures formed at different temperatures along the line of sight. Temperature-dependent damping may suggest some role of thermal conduction in the damping of Alfvén waves in the lower corona.
Pyrazolopyrimidine scaffold is one of the privileged heterocycles in drug discovery. This scaffold produced numerous biological activities in which anticancer is important one. Previous studies ...showed its importance in interactions with various receptors such as growth factor receptor, TGFBR2 gene, CDK2/cyclin E and Abl kinase, adenosine receptor, calcium-dependent Protein Kinase, Pim-1 kinase, Potent Janus kinase 2, BTK kinase, P21-activated kinase 1, extracellular signal-regulated kinase 2, histone lysine demethylase and Human Kinesin-5. However, there is a need of numerous studies for the discovery of target based potential compounds. The structure activity relationship studies may help to explore the generation of potential compounds in short time period. Therefore, in the present review we tried to explore the structural aspects of Pyrazolopyrimidine with their structure activity relationship against various targets for the development of potential compounds. The current review is the compilation of significant advances made on Pyrazolopyrimidines reported between 2015 and 2020.
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•Pyrazolo pyrimidine scaffold is one of the privileged heterocycles.•Target based potential compounds.•Signalling pathways plays an important role.•Structural insights and structure anticancer activity relationship.
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.
Aims. We focus on a polar coronal hole region to find any evidence of dissipation of propagating slow magneto-acoustic waves. Methods. We obtained time-distance and frequency-distance maps along the ...plume structure in a polar coronal hole. We also obtained Fourier power maps of the polar coronal hole in different frequency ranges in 171 Å and 193 Å passbands. We performed intensity distribution statistics in time domain at several locations in the polar coronal hole. Results. We find the presence of propagating slow magneto-acoustic waves having temperature dependent propagation speeds. The wavelet analysis and Fourier power maps of the polar coronal hole show that low-frequency waves are travelling longer distances (longer detection length) as compared to high-frequency waves. We found two distinct dissipation length scales of wave amplitude decay at two different height ranges (between 0–10 Mm and 10–70 Mm) along the observed plume structure. The dissipation lengths obtained at higher height range show some frequency dependence. Individual Fourier power spectrum at several locations show a power-law distribution with frequency whereas probability density function of intensity fluctuations in time show nearly Gaussian distributions. Conclusions. Propagating slow magneto-acoustic waves are getting heavily damped (small dissipation lengths) within the first 10 Mm distance. Beyond that waves are getting damped slowly with height. Frequency dependent dissipation lengths of wave propagation at higher heights may indicate the possibility of wave dissipation due to thermal conduction, however, the contribution from other dissipative parameters cannot be ruled out. Power-law distributed power spectra were also found at lower heights in the solar corona, which may provide viable information on the generation of longer period waves in the solar atmosphere.
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