MARCH8 downregulation modulates profibrotic responses including myofibroblast differentiation.

Interstitial lung diseases can result in poor patient outcomes, especially in idiopathic pulmonary fibrosis (IPF), a severe interstitial lung disease with unknown causes. The lack of treatment options requires further understanding of the pathological process/mediators. Membrane-associated RING-CH 8 (MARCH8) has been implicated in immune function regulation and inflammation, however, its role in the development of pulmonary fibrosis and particularly the fibroblast to myofibroblast transition (FMT) remains a gap in existing knowledge. In this study, we demonstrated decreased MARCH8 expression in patients with IPF compared with non-PF controls and in bleomycin-induced PF. TGF-ß dose- and time-dependently decreased MARCH8 expression in normal and IPF human lung fibroblast (HLFs), along with induction of FMT markers α-SMA, collagen type I (Col-1), and fibronectin (FN). Interestingly, overexpression of MARCH8 significantly suppressed TGF-ß-induced expression of α-SMA, Col-1, and FN. By contrast, the knockdown of MARCH8 using siRNA upregulated basal expression of α-SMA/Col-1/FN. Moreover, MARCH8 knockdown enhanced TGF-ß-induced FMT marker expression. These data clearly show that MARCH8 is a critical "brake" for FMT and potentially affects PF. We further found that TGF-ß suppressed MARCH8 mRNA expression and the proteasome inhibitor MG132 failed to block MARCH8 decrease induced by TGF-ß. Conversely, TGF-ß decreases mRNA levels of MARCH8 in a dose- and time-dependent manner, suggesting the transcriptional regulation of MARCH8 by TGF-ß. Mechanistically, MARCH8 overexpression suppressed TGF-ß-induced Smad2/3 phosphorylation, which may account for the observed effects. Taken together, this study demonstrated an unrecognized role of MARCH8 in negatively regulating FMT and profibrogenic responses relevant to interstitial lung diseases.NEW & NOTEWORTHY MARCH8 is an important modulator of inflammation, immunity, and other cellular processes. We found that MARCH8 expression is downregulated in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and experimental models of pulmonary fibrosis. Furthermore, TGF-ß1 decreases MARCH8 transcriptionally in human lung fibroblasts (HLFs). MARCH8 overexpression blunts TGF-ß1-induced fibroblast to myofibroblast transition while knockdown of MARCH8 drives this profibrotic change in HLFs. The findings support further exploration of MARCH8 as a novel target in IPF.

Modulatory effect of Artocarpus camansi on ILP-2, InR, and Imp-L2 genes of sucrose -induced diabetes mellitus in Drosophila melanogaster.

Diabetes mellitus continues to be a menace, being one of the five major causes of death in the world. In this study, the common fruit fly, Drosophila melanogaster, a well-studied genetic model organism for understanding molecular mechanisms of human diseases, and Artocarpus camansi (breadnut), an underutilized fruit, was used. This study was aimed at investigating the antihyperglycemic potentials of Artocarpus camansi fruit in sucrose-induced diabetic Drosophila melanogaster. Phytochemical screening was carried out after the fruit has been pulverized and freeze-dried. Total phenol content and total flavonoid content were carried out in vitro on the aqueous extract of Artocarpus camansi, and the result obtained showed that its phenol content is low, and its flavonoid content increases at increasing concentrations. Alpha-amylase inhibitory activity was carried out in vivo on sucrose-induced diabetic Drosophila melanogaster tissue. Gene expression profiling of Insulin-like peptide-2 (ILP-2), Insulin-like receptor (InR) and Ecdysone inducible gene L2 (Imp-L2) was carried out on trizol homogenate of Drosophila melanogaster tissue. In this study, Drosophila melanogaster was divided into nine groups. Group1 served as the basal control as they were fed with normal basal diet, group II served as the negative control which were fed with basal diet and 0.5 mL sucrose/100 mL distilled water, group III served as the positive control which were fed with basal diet 0.5 mL sucrose/100 mL distilled water and metformin, groups IV and V which were fed with basal diet and 0.1 and 1% Artocarpus camansi respectively, groups VI and VII were fed with basal diet, sucrose and 0.1 and 1% Artocarpus camansi respectively, groups VIII and IX served the purpose of the synergistic effect which were fed with basal diet, sucrose, metformin and 0.1 and 1% Artocarpus camansi respectively. All the groups were left for seven days. The experiment was conducted for 3 months and the fruit fly meals were changed every 5 days. Gene expression profiling results showed that the dietary inclusion of fruit downregulated the expression of ILP-2 and InR and upregulated the expression of Imp-L2 when the diabetic group were compared with the normal control. The results suggest that Artocarpus camansi fruit could possess antihyperglycemic properties and its use as a nutraceutical in the alleviation of diabetes should be encouraged.

The impacts of COVID-19 on environmental sustainability: A brief study in world context.

The novel outbreak of Coronavirus disease 19 (COVID-19) and the ensuing global pandemic in 2020, has brought with it a number of unprecedented side effects. This resulted in a number of measures, including state-mandated lockdowns, as well as restrictions to economic and social activity. The direct effects of these measures were felt in the economy, as well as in key institutions within society; however, there were also indirect results from these changes. This review article focuses on these indirect effects, towards sustainable environment. It points to the fact that the net effect has been positive; in terms of reduction in greenhouse emissions, oil exploration activities, and pollution. By extension, at-risk ecosystems have been given improved environmental quality. Taken together, the article traces the progression of the virus and ensuing pandemic, in order to better understand how the environment was sustained.

Effective production of succinic acid from coconut water (Cocos nucifera) by metabolically engineered Escherichia coli with overexpression of Bacillus subtilis pyruvate carboxylase.

Succinic acid is an important acid which is used in medicine and pharmaceutical companies. Metabolically engineered Escherichia coli strain was used for the effective production of succinic acid using Cocos nucifera water, which contained 5.00 ± 0.02 g/L glucose, 6.10 ± 0.01 g /L fructose and 6.70 ± 0.02 g /L sucrose. Fermentation of C. nucifera water with E. coli M6PM produced a final concentration of 11.78 ± 0.02 g/L succinic acid and yield of 1.23 ± 0.01 mol/mol, 0.66 ± 0.01 g/g total sugars after 72 h dual-phase fermentation in M9 medium while modeled sugar was 0.38 ± 0.02 mol/mol total sugars. It resulted in 72% of the maximum theoretical yield of succinic acid. Here we show that novel substrate of C. nucifera water resulted in effective production of succinic acid. These investigations unveil the importance of C. nucifera water as a substrate for the production of biochemicals.

CD146 T cells in lung cancer: its function, detection, and clinical implications as a biomarker and therapeutic target.

CD146 alternatively called melanoma cell adhesion molecule (MCAM), is a biomarker and therapeutic target of clinical significance. It is found on different cells including the endothelial cells and lymphocytes which participate in heterotypic and homotypic ligand-receptor. This review concentrated on the CD146 expression T cells (or lymphocytes) centering on Treg in lung cancer. Here, we have also considered the vigorous investigation of CD146 mainly acknowledged new roles, essential mechanisms and clinical implications of CD146 in cancer. CD146 has progressively become a significant molecule, particularly recognized as a novel biomarker, prognosis and therapy for cancer. Hence, targeting CD146 expression by utilization of methanol extracts of Calotropis procera leaf may be useful for the treatment of carcinogenesis.

Apatinib preferentially inhibits PC9 gefitinib-resistant cancer cells by inducing cell cycle arrest and inhibiting VEGFR signaling pathway.

BACKGROUND: Lung cancer is one of the most common and deadly tumors around the world. Targeted therapy for patients with certain mutations, especially by use of tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR), has provided significant benefit to patients. However, gradually developed resistance to the therapy becomes a major challenge in clinical practice and an alternative to treat such patients is needed. Herein, we report that apatinib, a novel anti-angiogenic drug, effectively inhibits obtained gefitinib-resistant cancer cells but has no much effect on their parental sensitive cells. METHODS: Gefitinib-resistant lung cancer cell line (PC9GR) was established from its parental sensitive line (PC9) with a traditional EGFR mutation after long time exposure to gefitinib. Different concentrations of apatinib were used to treat PC9, PC9GR, and other two lung cancer cell lines for its anti-growth effects. RNA sequencing was performed on PC9, PC9GR, and both after apatinib treatment to detect differentially expressed genes and involved pathways. Protein expression of key cycle regulators p57, p27, CDK2, cyclin E2, and pRb was detected using Western blot. Xenograft mouse model was used to assess the anti-tumor activity of apatinib in vivo. RESULTS: The established PC9GR cells had over 250-fold increased resistance to gefitinib than its sensitive parental PC9 cells (IC50 5.311 ± 0.455 µM vs. 0.020 ± 0.003 µM). The PC9GR resistance cells obtained the well-known T790M mutation. Apatinib demonstrated much stronger ( ~ fivefold) growth inhibition on PC9GR cells than on PC9 and other two lung cancer cell lines, A549 and H460. This inhibition was mostly achieved through cell cycle arrest of PC9GR cells in G1 phase. RNA-seq revealed multiple changed pathways in PC9GR cells compared to the PC9 cells and after apatinib treatment the most changed pathways were cell cycle and DNA replication where most of gene activities were repressed. Consistently, protein expression of p57, CDK2, cyclin E2, and pRb was significantly impacted by apatinib in PC9GR cells. Oral intake of apatinib in mouse model significantly inhibited establishment and growth of PC9GR implanted tumors compared to PC9 established tumors. VEGFR2 phosphorylation in PC9GR tumors after apatinib treatment was significantly reduced along with micro-vessel formation. CONCLUSIONS: Apatinib demonstrated strong anti-proliferation and anti-growth effects on gefitinib resistant lung cancer cells but not its parental sensitive cells. The anti-tumor effect was mostly due to apatinib induced cell cycle arrest and VEGFR signaling pathway inhibition. These data suggested that apatinib may provide a benefit to patients with acquired resistance to EGFR-TKI treatment.

Alveolar type 2 progenitor cells for lung injury repair.

Alveolar type 2 progenitor cells (AT2) seem closest to clinical translation, specifying the evidence that AT2 may satisfactorily control the immune response to decrease lung injury by stabilizing host immune-competence and a classic and crucial resource for lung regeneration and repair. AT2 establish potential in benefiting injured lungs. However, significant discrepancies linger in our understanding vis-à-vis the mechanisms for AT2 as a regime for stem cell therapy as well as essential guiding information for clinical trials, including effectiveness in appropriate pre-clinical models, safety, mostly specifications for divergent lung injury patients. These important gaps shall be systematically investigated prior to the vast therapeutic perspective of AT2 cells for pulmonary diseases can be considered. This review focused on AT2 cells homeostasis, pathophysiological changes in the pathogenesis of lung injury, physiological function of AT2 cells, apoptosis of AT2 cells in lung diseases, the role of AT2 cells in repairing processes after lung injury, mechanism of AT2 cells activation promote repairing processes after lung injury, and potential therapy of lung disease by utilizing the AT2 progenitor cells. The advancement remains to causally connect the molecular and cellular alteration of AT2 cells to lung injury and repair. Conclusively, it is identified that AT2 cells can convert into AT1 cells; but, the comprehensive cellular mechanisms involved in this transition are unrevealed. Further investigation is mandatory to determine new strategies to prevent lung injury.

Enhanced production of succinic acid from methanol-organosolv pretreated Strophanthus preussii by recombinant Escherichia coli.

A biorefinery process for high yield production of succinic acid from biomass sugars was investigated using recombinant Escherichia coli. The major problem been addressed is utilization of waste biomass for the production of succinic acid using metabolic engineering strategy. Here, methanol extract of Strophanthus preussii was used for fermentation. The process parameters were optimized. Glucose (9 g/L), galactose (4 g/L), xylose (6 g/L) and arabinose (0.5 g/L) were the major sugars present in the methanol extract of S. preussii. E. coli K3OS with overexpression of soluble nucleotide pyridine transhydrogenase sthA and mutation of lactate dehydrogenase A (ldhA), phosphotransacetylase acetate kinase A (pta-ackA), pyruvate formate lyase B (pflB), pyruvate oxidase B (poxB), produced a final succinic acid concentration of 14.40 g/L and yield of 1.10 mol/mol total sugars after 72 h dual-phase fermentation in M9 medium. Here, we show that the maximum theoretical yield using methanol extracts of S. preussii was 64%. Hence, methanol extract of S. preussii could be used for the production of biochemicals such as succinate, malate and pyruvate.

Efficient production of succinic acid from Palmaria palmata hydrolysate by metabolically engineered Escherichia coli.

Succinic acid, a C4 dicarboxylic acid is used in many fields such as food, agriculture, pharmaceutical and polymer industries. In this study, microbial production of succinic acid from Palmaria palmata was investigated for the first time. In engineered Escherichia coli KLPPP, lactate dehydrogenase, pyruvate formate lyase, phosphotransacetylase-acetate kinase and pyruvate oxidase genes were deleted while phosphoenolpyruvate carboxykinase was overexpressed. The recombinant exhibited higher molar yield of succinic acid on galactose (1.20±0.02mol/mol) than glucose (0.48±0.03mol/mol). The concentration and molar yield of succinic acid were 22.40±0.12g/L and 1.13±0.02mol/mol total sugar respectively after 72h dual phase fermentation from P. palmata hydrolysate which composed of glucose (12.57±0.17g/L) and galactose (18.03±0.10g/L). The results demonstrate that P. palmata red macroalgae biomass represents a novel and an economically alternative feedstock for biochemicals production.

Effective degradation of rhodamine B by electro-Fenton process, using ferromagnetic nanoparticles loaded on modified graphite felt electrode as reusable catalyst: in neutral pH condition and without external aeration.

Polytetrafluoroethylene/ferromagnetic nanoparticle/carbon black (PTFE/MNP/CB)-modified graphite felt (GF) was successfully applied as cathode for the mineralization of rhodamine B (RhB) in electro-Fenton (EF) process. The modified cathode showed high decolorization efficiency for RhB solution even in neutral pH condition and without external aeration, achieving nearly complete decolorization and 89.52 % total organic carbon (TOC) removal after 270-min oxidation with the MNP load 1.2 g at 50 A/m(2). Moreover, the operational parameters (current density, MNP load, initial pH, and airflow rate) were optimized. After that, adsorption isotherm was also conducted to compare the absorption quantity of CB and carbon nanotube (CNT). Then, the surface morphologies of MNPs were characterized by transmission electron microscope (TEM), energy-dispersive X-ray detector (EDX), and Fourier transform infrared spectroscopy (FTIR); and the modified cathode was characterized by SEM and contact angle. Finally, the stability and reusability of modified cathode were tested. Result uncovered that the PTFE/MNP/CB-modified cathode has the potential for industrial application and the solution after treatment was easily biodegradable.

Efficient degradation of rhodamine B using modified graphite felt gas diffusion electrode by electro-Fenton process.

The electro-Fenton (EF) process treatment of 0.1-M (rhodamine B) RhB solution was studied with different graphite cathode materials, and graphite felt (GF) was selected as a promising material in further investigation. Then, the degradation performances of gas diffusion electrode (GDE) and graphite felt (GF) were compared, and GDE was confirmed to be more efficient in RhB removal. The operational parameters such as Fe(2+) dosage and current density were optimized, and comparison among different modified methods-polytetrafluoroethylene-carbon black (PTFE-CB), polytetrafluoroethylene-carbon nanotube (PTFE-CNT), electrodeposition-CB, and electrodeposition-CNT-showed 98.49 % RhB removal by PTFE-CB-modified cathode in 0.05 M Na2SO4 at a current density of 50 A/m(2) and an air flow rate of 1 L/min after 20 min. Meanwhile, after cathode modified by PTFE-CB, the mineralization efficiency and mineralization current efficiency performed absolutely better than the pristine one. Cyclic voltammograms, SEM images, contact angles, and BET surface area were carried out to demonstrate stronger current responses and higher hydrophilicity of GF after modified. The value of biochemical oxygen demand/chemical oxygen demand (BOD5/COD) increased from 0.049 to 0.331 after 90-min treatment, suggesting the solution was biodegradable, and the modified cathode was confirmed to be stable after ten circle runs. Finally, a proposed degradation pathway of RhB was put forward.