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Background: Methotrexate (MTX) is used as anchor drug for patients with early and established rheumatoid arthritis (RA). Vitamin K2 administration was also reported to be associated with decreased disease activity in RA. Objectives: Immunosuppressive pharmacodynamics of vitamin K2 combined with MTX was investigated. Methods: Mitogen‐activated peripheral blood mononuclear cells (PBMCs) were used to evaluate immunosuppressive pharmacodynamics of drugs in vitro. Results: Vitamin K2 alone dose‐dependently suppressed T cell mitogen‐activated proliferation of PBMCs of both healthy subjects and RA patients. 446.5 and 2232.5 ng/mL vitamin K2 significantly decreased the IC50 values of MTX on the proliferation of PBMCs of RA patients, with little influences on the pharmacodynamics of MTX in the healthy PBMCs. 4465 ng/mL vitamin K2 potentiated the pharmacodynamics of MTX in both RA patients and healthy PBMCs. The additional effects of vitamin K2 to potentiate the suppressive effects of MTX seemed not to be related to the regulation of CD4+CD25+ T cells or CD4+CD25+Foxp3+ Treg cells. MTX alone at 100 ng/mL significantly decreased the percentage of CD4+ T cells in PBMCs of healthy subjects (p < 0.001) with a slight influence in that of RA patients (not significant) and the combination did not show synergistic inhibitory effect. Vitamin K2 alone tended to suppress the secretion of IL‐17, IFN‐γ, and TNF‐α from the activated PBMCs of RA patients with smaller influences on the cytokine productions from healthy PBMCs. These additional effects of vitamin K2 were also observed in combination with MTX. Conclusion: The above information may partially elucidate the potentiation effects of vitamin K2 on the immunosuppressive efficacy of MTX. [ABSTRACT FROM AUTHOR]

Sinomenine (SN) is a plant‐derived alkaloid isolated from Caulis Sinomenii. It has been approved by the State Food and Drug Administration of China for treating rheumatoid arthritis (RA) nearly 20 years ago. To investigate the anti‐RA mechanism of SN, a lot of scholars reported the immunosuppressive effect of SN on T lymphocytes. We continued to evaluate the suppressive function of SN by using human peripheral blood mononuclear cells (PBMCs) isolated from RA patients. As the positive control, 10 ng/ml of methylprednisolone (MP) showed the antiproliferation effect on mitogen‐activated PBMCs of RA patients significantly (*p <.05). Meanwhile, MP decreased the frequency of CD4+ CD25+ T cells and suppressed the secretion of inflammatory Th1/Th2/Th17 cytokines such as IL‐4, IL‐6, IL‐10, IL‐17, IFN‐γ, and TNF‐α. However, SN at concentrations of 0.3–30 μM, showed little suppressive effects on the proliferation of PBMCs of RA patients. We did not observe any suppressive effects of SN on percentages of CD4+ T cells and CD4+ CD25+ T cells in the mitogen‐activated PBMCs of RA patients. The influence of SN on the percentage of CD4+ CD25+ Foxp3+ T cells was also limited. Finally, even 30 μM of SN did not influence the secretion of Th1/Th2/Th17 cytokine significantly. The present study provided evidence that anti‐RA mechanism of SN seems not to be related with the suppressive effects on peripheral T cells. [ABSTRACT FROM AUTHOR]

Natural compound tetrandrine was reported to inhibit the proliferation of T cells by inhibiting activation of NF-κB. Chemically, isotetrandrine differs from tetrandrine only in the stereochemistry at the chiral centers. The present study aimed to compare their anti-proliferation effects on human T cells with a focus on NF-κB. The IC50 values of tetrandrine against MOLT-4 cells, MOLT-4/DNR cells, and concanavalin A-activated peripheral blood mononuclear cells of healthy subjects and dialysis patients were 4.43 ± 0.22, 3.62 ± 0.22, 1.91 ± 0.22 and 3.03 ± 0.28 μM, respectively. Whereas, the IC50 values of isotetrandrine against the above immune cells were 2.19 ± 0.27, 2.28 ± 0.33, 1.29 ± 0.14 and 1.55 ± 0.26 μM, respectively. The inhibitory effect of isotetrandrine against the proliferation of T cells was stronger than that of tetrandrine significantly (p < 0.05). Molecular mechanism investigation showed that 10 μM of isotetrandrine largely decreased the expression of p-NF-κB and NF-κB in both MOLT-4 and MOLT-4/DNR T cells (p < 0.05), whereas 10 μM of tetrandrine slightly inhibited the phosphorylation of p-NF-κB with little influence on the expression of NF-κB. Taken together, absolute configurations of tetrandrine and isotetrandrine are suggested to influence on their anti-proliferation effects in human T cells via different regulation of NF-κB. [ABSTRACT FROM AUTHOR]

Dry triboelectric separation of coal depends on tribocharge difference of the coal and gangue minerals. A suitable tribocharger material which makes the coal and minerals tribocharged of opposite polarity is of great importance for triboelectric separation. In this paper, the composition of coal was analyzed by x-ray diffraction (XRD), and the triboelectric characteristics of coal and other ash-forming minerals were tested using stainless steel (SS), polyvinyl chloride (PVC), pentatricopeptide repeats (PPR), polyfluortetraethylene (PPFT), and polymethyl methacrylate (PMMA) tribochargers in lab triboelectric unit. The charge−mass ratio of coal and mineral particles were presented and evaluated. Infrared spectroscopy was adopted to analyze the different tribocharge properties between clean coal and minerals. The results show that the gangue minerals in coal are mainly pyrite, kaolin, calcite, dolomite, and quartz. The conductive mineral had the lowest chargeability, especially tribocharged with conductive material. Compared with the inorganic surface, the organic surface is easy to lose electrons and charge positively. According to the triboelectric characteristics of coal and minerals, PMMA is more suitable as tribocharger material for triboelectric separation of pulverized coal compared with PVC, PPFT, PPR, and SS. The better separation efficiency of Tai Xi anthracite coal is obtained by using PMMA tribocharger. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the expression of P-glycoprotein in T-cell subpopulations of lymphocytes from adult patients with refractory glomerulonephritis (GN)., Materials and Methods: Flow cytometry was used to analyze the T-cell subpopulations of lymphocytes from adult patients with refractory GN and healthy individuals. The CD243 antibody marked the membrane P-glycoprotein of immune cells., Results: The mean ± standard deviation (SD) values of percentages of CD3 + , CD3 + CD4 + , CD3 + CD8 + cells in lymphocytes from patients with refractory GN were 63.94 ± 26.98, 55.16 ± 4.78, and 37.79 ± 6.01%, respectively. These values in healthy individuals were 74.88 ± 3.75, 56.60 ± 9.22, and 34.20 ± 5.21%, respectively. No significant differences were observed between the patients with refractory GN and healthy individuals. The mean ± SD values of percentages of CD3 + CD4 + CD243 + and CD3 + CD8 + CD243 + cells in the lymphocytes of patients with refractory GN were 0.14 ± 0.11 and 0.11 ± 0.07%, respectively. These values in healthy individuals were 0.05 ± 0.02 and 0.04 ± 0.02%, respectively. The difference in CD3 + CD8 + CD243 + percentage between patients with refractory GN and healthy individuals was significant (p = 0.0216)., Conclusion: These findings suggest that P-glycoprotein expression on CD3 + CD8 + T cells is a promising marker and a suitable target of drug resistance in patients with refractory GN.

Objective: Despite the use of renin-angiotensin system blockade and immunosuppressive drugs, including corticosteroids, the current treatment regimens for Immunoglobulins A nephropathy (IgAN) are severely limited. The proliferation of mesangial cell and deposition of deglycosylated human IgA1 immune complex are the most common pathologic features of IgAN. We examined the tetrandrine potential of suppressing the proliferation of mesangial cells and explored its underlying mechanisms with a focus on IgA receptor/MAPK/NF-κB signaling pathway. Methods: Standard human IgA (native IgA) were enzymatically desialylated (deS IgA) or further degalactosylated (deS/deGal IgA) using neuraminidase and β -galactosidase. Rat glomerular mesangial cells (HBZY-1) and human renal mesangial cells (HRMC) stimulated by IgA were used to observe the suppressive effect of tetrandrine. The MTT assay was used to detect the cell viability. The protein expression of IgA receptor/MAPK/NF-κB signaling pathway was examined by Western blot. Cell cycle analysis was measured by flow cytometer. Results: Native IgA and deS IgA showed limited stimulation effect on both HBZY-1 cells and HRMCs, whereas deS/deGal IgA significantly stimulated the proliferation of both HBZY-1 cells and HRMCs ( p < 0.05). Compared with non-stimulation of deS/deGal IgA, 1-3 μM of tetrandrine had stronger inhibitory effect on the proliferation of HBZY-1 cells and HRMCs with the stimulation of deS/deGal IgA ( p < 0.05), suggesting that tetrandrine possibly inhibited the proliferation of mesangial cells induced by deglycosylated human IgA1 specifically. Molecular mechanism study revealed that tetrandrine decreased the expression of IgA1 receptor, CD71 and β4GALT1, and inhibited the activation of MAPK/NF-κB significantly ( p < 0.05). Moreover, these inhibitory effect of tetrandrine caused cell cycle arrest and stopped the cell growth in the S phase companied with the upregulating of cyclin A2 and downregulating of cyclin D1. Conclusion: Taken together, tetrandrine inhibited the proliferation of mesangial cells induced by enzymatically deglycosylated human IgA1 via IgA receptor/MAPK/NF-κB signaling pathway. Based on these potential molecular mechanisms, tetrandrine would be an appealing therapeutic option for IgAN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Song, Chen, Jin, Xue, Min, Wang and You.)

Antioxidant system is of great importance for organisms to regulate the level of excessive reactive oxygen species (ROS) under the environmental stresses including antibiotics stress. Effects of norfloxacin (NOR) on cystathionine-β-synthase (CBS), nitric oxide synthase (NOS) and antioxidant enzymes were investigated, and interaction between NO and H 2 S and their regulation on the antioxidant system of Vibrio alginolyticus under NOR were determined as well in the present study. After treated with 2 µg/mL NOR (1/2 MIC), CBS content, H 2 S and NO contents decreased while H 2 O 2 accumulation and the antioxidant-related genes mRNA level increased. Additionally, the endogenous H 2 S content in V. alginolyticus was increased by the exogenous NO, while H 2 O 2 accumulation and the relative expression level of SOD (Superoxide dismutase gene) decreased under exogenous NO or H 2 S. And the content of endogenous NO and NOS in V. alginolyticus increased under the exogenous H 2 S as well. Taken together, these results showed that anti-oxidative ability in V. alginolyticus was respectively enhanced by the gas molecules of H 2 S and NO under NOR-induced stress, and there may be a crosstalk regulative mechanism between H 2 S and NO. These results lay a foundation for the research of regulation network of H 2 S and NO, and provide a hint to synthesize anti-vibrio drugs in the future., Competing Interests: The authors declare there are no competing interests., (©2021 Chen et al.)

Background: Methotrexate (MTX) is used as anchor drug for patients with early and established rheumatoid arthritis (RA). Vitamin K 2 administration was also reported to be associated with decreased disease activity in RA., Objectives: Immunosuppressive pharmacodynamics of vitamin K 2 combined with MTX was investigated., Methods: Mitogen-activated peripheral blood mononuclear cells (PBMCs) were used to evaluate immunosuppressive pharmacodynamics of drugs in vitro., Results: Vitamin K 2 alone dose-dependently suppressed T cell mitogen-activated proliferation of PBMCs of both healthy subjects and RA patients. 446.5 and 2232.5 ng/mL vitamin K 2 significantly decreased the IC 50 values of MTX on the proliferation of PBMCs of RA patients, with little influences on the pharmacodynamics of MTX in the healthy PBMCs. 4465 ng/mL vitamin K 2 potentiated the pharmacodynamics of MTX in both RA patients and healthy PBMCs. The additional effects of vitamin K 2 to potentiate the suppressive effects of MTX seemed not to be related to the regulation of CD4 + CD25 + T cells or CD4 + CD25 + Foxp3 + Treg cells. MTX alone at 100 ng/mL significantly decreased the percentage of CD4 + T cells in PBMCs of healthy subjects (p < 0.001) with a slight influence in that of RA patients (not significant) and the combination did not show synergistic inhibitory effect. Vitamin K 2 alone tended to suppress the secretion of IL-17, IFN-γ, and TNF-α from the activated PBMCs of RA patients with smaller influences on the cytokine productions from healthy PBMCs. These additional effects of vitamin K 2 were also observed in combination with MTX., Conclusion: The above information may partially elucidate the potentiation effects of vitamin K 2 on the immunosuppressive efficacy of MTX., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)