The interplay of co-infections in shaping COVID-19 severity: Expanding the scope beyond SARS-CoV-2.

High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co- infections by other pathogens and their involvement in the severity of COVID-19.

Gut-brain axis interplay via STAT3 pathway: Implications of Helicobacter pylori derived secretome on inflammation and Alzheimer's disease.

Helicobacter pylori is a pathogenic bacterium that causes gastritis and gastric carcinoma. Besides gastric complications its potential link with gut-brain axis disruption and neurological disorders has also been reported. The current study investigated the plausible role and its associated molecular mechanism underlying H. pylori mediated gut-brain axis disruption and neuroinflammation leading to neurological modalities like Alzheimer's disease (AD). We have chosen the antimicrobial resistant and susceptible H. pylori strains on the basis of broth dilution method. We have observed the increased inflammatory response exerted by H. pylori strains in the gastric as well as in the neuronal compartment after treatment with Helicobacter pylori derived condition media (HPCM). Further, elevated expression of STAT1, STAT3, and AD-associated proteins- APP and APOE4 was monitored in HPCM-treated neuronal and neuron-astrocyte co-cultured cells. Excessive ROS generation has been found in these cells. The HPCM treatment to LN229 causes astrogliosis, evidenced by increased glial fibrillary acidic protein. Our results indicate the association of STAT3 as an important regulator in the H. pylori-mediated pathogenesis in neuronal cells. Notably, the inhibition of STAT3 by its specific inhibitor, BP-1-102, reduced the expression of pSTAT3 and AD markers in neuronal compartment induced by HPCM. Thus, our study demonstrates that H. pylori infection exacerbates inflammation in AGS cells and modulates the activity of STAT3 regulatory molecules. H. pylori secretome could affect neurological compartments by promoting STAT3 activation and inducing the expression of AD-associated signature markers. Further, pSTAT-3 inhibition mitigates the H. pylori associated neuroinflammation and amyloid pathology.

SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1.

SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated necrotic cell death in E protein transfected cells. Our study revealed the role of the necroptotic marker RIPK1 in cell death. Additionally, inhibition of RIPK1 by its specific inhibitor Nec-1s exhibits recovery from cell death and inflammation manifested by reduced phosphorylation of NFκB. The E-transfected cells' conditioned media induced inflammation with differential expression of inflammatory markers compared to direct transfection in the gastrointestinal-lung axis. In conclusion, SARS-CoV-2 E mediates inflammation and necroptosis through RIPK1, and the E-expressing cells' secretion can modulate the gastrointestinal-lung axis. Based on the data of the present study, we believe that during severe COVID-19, necroptosis is an alternate mechanism of cell death besides ferroptosis, especially when the disease is not associated with drastic increase in serum ferritin.

Evaluation for substitution of stem bark with small branches of Cassia fistula Linn for traditional medicinal uses: A comparative chemical profiling studies by HPLC, LC-MS, GC-MS.

Background: The Aim of the present research article is to proposing a conservative approach for the Cassia fistula by using of small branches instead of stem bark because of plant has many important chemical constituents which show different medicinal activity so consumption of plant is high. We studied here Comparative preliminary phytochemical screening test of the ethanol extract and aqueous extract of the stem bark and small branches of Cassia fistula obtained by cold maceration process. Physicochemical analysis of Cassia fistula was done to ascertain the quality of the raw material used in the study. Successive soxhlet extraction method used for the successive extraction of stem bark and small branches with different solvents for comparative chemical profile study by HPLC, LCMS, and GCMS. Molecular Docking Interaction of Abundant Medicinal Phytochemicals in the Liquid Chromatography-Mass Spectrometry (LC-MS) Analysis Data of C. fistula with the L. donovani Drug Target Proteins and Pancreatic lipase colipase target protein. Result: The pH of the small branches was found slightly higher as compared to stem bark and the percentage of other parameters like total ash content, acid insoluble ash, loss on drying at 105 °C, water soluble extractive and alcohol soluble extractive values were found fewer in the small branches as compare to stem bark of the plant. It was observed that the number of peaks in stem bark and small branches of the plant sample were almost similar and the retention time of each peak in stem bark was coincide with the retention of small branches of the sample. Therefore, similarity was observed in stem bark and small branches of the Cassia fistula plant in HPLC, LC-MS and GC-MS. The results obtained from HPLC analysis shows that stem bark contains 0.0084% and small branches having 0.0257% of rhein in Cassia fistula. Compounds 3, 9 and 12 are present in Stem bark as well as small branches of C. fistula and Compounds 22, 32 and 37 are present in small branches only. All the compounds have very good binding energy (Kcal/mol) with the respective target proteins. Conclusion: The small branches have more active chemical constituents than stem bark against particular target proteins.

Evaluation of Substitution of Small Branches with Roots of Desmodium gangeticum (Physicochemical Analysis, HPLC, and GC-MS Profiling) and In Silico Study of Pterocarpans for Pharmacological Target.

The present research article proposes a conservative approach for the Desmodium gangeticum by using small branches instead of roots because the plant has many important chemical constituents that show different medicinal activity, so the plant's consumption is high. We studied here comparative preliminary phytochemical screening test and physicochemical analysis. The successive soxhlet extraction method was used for the successive extraction of roots and small branches with different solvents for comparative chemical profile study by HPLC and GC-MS. It was observed that many peaks in roots and small branches of the plant sample were almost similar, and the retention time of each peak in roots coincided with the retention of small branches of the sample. Therefore, the similarity was observed in roots and small branches of the Desmodium gangeticum plant in HPLC and GC-MS. The results obtained from HPLC analysis show that roots contain 0.00116% and small branches have 0.00026% of caffeic acid in Desmodium gangeticum. The small branches may have almost similar active chemical constituents like roots. In silico molecular docking study revealed that this plant's principal chemical constituents, pterocarpans, could be inhibitors of protein tyrosine phosphate kinase.

Identification and estimation of bioactive constituents Negundoside, Berberine chloride, and Marmelosin by HPLC and HPTLC for development of quality control protocols for Ayurvedic medicated oil formulation.

BACKGROUND: Anu Taila is an ancient medicated oil Ayurvedic preparation that is commonly used for nasya karma. It contains more than 25 herbs and goat milk as per the Ayurvedic Formulary of India (AFI). It strengthens the neck, shoulder, and chest muscles and improves the capacity of sense organs. It delays the aging process and reduces hair fall. Recent studies showed that it is also useful in COVID-19. In the current study, an attempt to develop quality control protocols and evaluate the standardization parameters like refractive index, iodine value, saponification value, peroxide value, acid value, rancidity, HPTLC fingerprint profile along with major bioactive compound and quantification of Berberine chloride, Negundoside, and Marmelosin by HPLC. Establishing quality protocol and standard parameters like physicochemical parameters and estimation of bioactive compounds of this preparation is significant for quality control. RESULTS: In this study, HPTLC identifies bioactive chemical compounds like Berberine chloride, Marmelosin, Negundoside, glycyrrhizin, and para hydroxybenzoic acid (PHBA), Lupeol, Embelin, and Solasodine, which were present in the Anu Taila formulation. HPLC was used to estimate the bioactive marker compounds Negundoside, Berberine chloride, and Marmelosin were present in the Anu Taila formulation. The quantitative evaluation of Berberine chloride (0.0013%), Marmelosin (0.0366%), Negundoside (0.0086%) is present in Anu Taila formulation. CONCLUSION: The study reveals that sufficient quality control parameters were followed during the preparation of the formulation. Physicochemical analysis was carried out as per the guidelines of Ayurvedic Pharmacopeia of India. HPTLC and HPLC profiles generated in this particular study can be considered as a preliminary tool ascertaining the authenticity of Anu Taila.

Estimation of Withaferin-A by HPLC and standardization of the Ashwagandhadi lehyam formulation.

Standardization is an important measurement for ensuring the quality control of herbal drugs. It has become essential to develop reliable, specific and sensitive quality control methods. Ashwagandhadi lehyam is an important Ayurvedic formulation containing Withania somnifera L., as one of the prime ingredient of formulation. The present study was undertaken to develop standardization parameters for Ashwagandhadi lehyam. Evaluation of various standardization parameters like organoleptic characters, Physico-chemical evaluation, HPTLC finger print profiling along with dominant bioactive markers and estimation of bioactive markers Withaferin-A by HPLC. The Rf value of Withaferin-A 0.35 and Withanolide-A 0.45 is in formulation and reference standards were found comparable under UV light at 254 nm and 540 nm. The HPLC chromatogram of Ashwagandhadi lehyam and standard Withaferin-A showed at Rt of 5.015 and 5.050 min. The percentage of Withaferin-A was 0.092% present in Ashwagandhadi lehyam formulation. Bioactive markers are characteristic to the ingredients or botanicals to identify the presence of ingredients in formulation easily. The presence of bioactive markers is possible and its verification through the HPTLC fingerprint profile and quantification of biomarker by HPLC are the best ways to identify evaluate the quality of the finished formulation in the course of development of a standardization protocol for quality control of Ayurvedic formulation.

Estimation of heavy metals in commonly used medicinal plants: a market basket survey.

Popularity of herbal drugs is increasing all over the world because of lesser side effects as compared to synthetic drugs besides it cost effectiveness and easy availability to poor people particularly in developing countries. Keeping in view the increased market demand of herbal drugs, it is essential to ensure their chemical quality prior to use. Raw drugs and herbs are usually collected from different places, which might be contaminated with various contaminants. It is pertinent to estimate the levels of heavy metals and other micronutrients, which could be affected by their presence in the surrounding environments. Heavy metals are known to pose a potential threat to terrestrial and aquatic biota. Keeping this in view, samples of ten plants or plant parts used in drug making were collected from local markets of Punjab for heavy metal and micronutrient estimation. It was found that the samples were contaminated having cadmium, lead, chromium, iron, manganese, and zinc. The highest mean level of cadmium (23.1 µg/kg) was found in Haritaki sample. Chromium concentration of the plant samples ranged between 7.25 and 1.34 µg/kg with the highest values was in Daruharidra and lowest in Pippali. The levels of these heavy metals were within permissible limits.

Adsorptive removal of heavy metals from aqueous solution by treated sawdust (Acacia arabica).

The removal of Cr(VI), Pb(II), Hg(II) and Cu(II), by treated sawdust has been found to be concentration, pH, contact time, adsorbent dose and temperature dependent. The adsorption parameters were determined using both Langmuir and Freundlich isotherm models. Adsorption capacity for treated sawdust, i.e. Cr(VI) (111.61 mg/g), Pb(II) (52.38 mg/g), Hg(II) (20.62 mg/g), and Cu(II) (5.64 mg/g), respectively. Surface complexation and ion exchange are the major removal mechanisms involved. The adsorption isotherm studies clearly indicated that the adsorptive behaviour of metal ions on treated sawdust satisfies not only the Langmuir assumptions but also the Freundlich assumptions. The applicability of Lagergren kinetic model has also been investigated. The adsorption follows first-order kinetics. Thermodynamic constant (k(ad)), standard free energy (DeltaG degrees ), enthalpy (DeltaH degrees ) and entropy (DeltaS degrees ) were calculated for predicting the nature of adsorption. The percentage adsorption increases with pH to attain a maximum at pH 6 and thereafter it decreases with further increase in pH. The results indicate the potential application of this method for effluent treatment in industries and also provide strong evidence to support the adsorption mechanism proposed.

Adsorption of Pb(II) and Cd(II) metal ions from aqueous solutions by mustard husk.

The adsorption of Pb(II) and Cd(II) metal ions on mustard husk has been found to be concentration, pH, contact time, adsorbent dose and temperature dependent. The adsorption parameters were determined using Langmuir and Freundlich isotherm models. The adsorption isotherm studies clearly indicated that the adsorptive behavior of Pb(II) and Cd(II) metal ions on mustard husk satisfies not only the Langmuir assumptions but also the Freundlich assumptions, i.e. multilayer formation on the surface of the adsorbent with an exponential distribution of site energy. Ion exchange and surface complexation are the major adsorption mechanisms involved. The applicability of Lagergren kinetic model has also been investigated. Thermodynamic constant (k(ad)), free energy change (DeltaG), enthalpy change (DeltaH) and entropy change (DeltaS) were calculated for predicting the nature of adsorption. The results indicate the potential application of this method for effluent treatment in industries and also provide strong evidence to support the adsorption mechanism proposed.

Removal of heavy metal ions from aqueous solutions using carbon aerogel as an adsorbent.

The removal of Cd(II), Pb(II), Hg(II), Cu(II), Ni(II), Mn(II) and Zn(II) by carbon aerogel has been found to be concentration, pH, contact time, adsorbent dose and temperature dependent. The adsorption parameters were determined using both Langmuir and Freundlich isotherm models. Surface complexation and ion exchange are the major removal mechanisms involved. The adsorption isotherm studies clearly indicated that the adsorptive behaviour of metal ions on carbon aerogel satisfies not only the Langmuir assumptions but also the Freundlich assumptions, i.e. multilayer formation on the surface of the adsorbent with an exponential distribution of site energy. The applicability of the Lagergren kinetic model has also been investigated. Thermodynamic constant (K(ad)), standard free energy (DeltaG(0)), enthalpy (DeltaH(0)) and entropy (DeltaS(0)) were calculated for predicting the nature of adsorption. The results indicate the potential application of this method for effluent treatment in industries and also provide strong evidence to support the adsorption mechanism proposed.