The impact of microplastics on sulfur REDOX processes in different soil types: A mechanism study.

Microplastics can potentially affect the physical and chemical properties of soil, as well as soil microbial communities. This could, in turn, influence soil sulfur REDOX processes and the ability of soil to supply sulfur effectively. However, the specific mechanisms driving these effects remain unclear. To explore this, soil microcosm experiments were conducted to assess the impacts of polystyrene (PS) and polyphenylene sulfide (PPS) microplastics on sulfur reduction-oxidation (REDOX) processes in black, meadow, and paddy soils. The findings revealed that PS and PPS most significantly decreased SO42- in black soil by 9.4%, elevated SO42- in meadow soil by 20.8%, and increased S2- in paddy soil by 20.5%. PS and PPS microplastics impacted the oxidation process of sulfur in soil by influencing the activity of sulfur dioxygenase, which was mediated by α-proteobacteria and γ-proteobacteria, and the oxidation process was negatively influenced by soil organic matter. PS and PPS microplastics impacted the reduction process of sulfur in soil by influencing the activity of adenosine-5'-phosphosulfate reductase, sulfite reductase, which was mediated by Desulfuromonadales and Desulfarculales, and the reduction process was positively influenced by soil organic matter. In addition to their impacts on microorganisms, it was found that PP and PPS microplastics directly influenced the structure of soil enzymes, leading to alterations in soil enzyme activity. This study sheds light on the mechanisms by which microplastics impact soil sulfur REDOX processes, providing valuable insights into how microplastics influence soil health and functioning, which is essential for optimizing crop growth and maximizing yield in future agricultural practices.

The capillary-leakage syndrome caused by glyphosate poisoning: a case report.

Glyphosate is widely used in agriculture even though it can cause self-poisoning, inducing gastrointestinal disturbance, acute respiratory distress syndrome, arrhythmia, renal failure, and even death. Case presentation: The authors present a case of glyphosate poisoning in a patient who developed capillary-leak syndrome, severe metabolic acidosis, and shock. After treatment with hemoperfusion and continuous renal replacement therapy, the patient was extubated after 7 days and transferred out of the intensive care unit after 10 days. Clinical discussion: Severe glyphosate poisoning can lead to multiple organ failure and systemic capillary leak syndrome. Clinical manifestations of systemic capillary leak syndrome included hemoconcentration, increased hematocrit, hypoalbuminemia, interstitial fluid accumulation, and refractory hypotension. Substantial improvement of capillary leakage was observed only gradually after initiation of early continuous renal replacement therapy, plasma infusion, and application of ulinastatin. Conclusions: This case report highlights the life-threatening nature of glyphosate poisoning. Aggressive treatment and careful monitoring of complications are required, particularly in patients at risk of capillary leakage syndrome.

Effect of Hepatocyte Growth Factor-Transfected Human Umbilical Cord Mesenchymal Stem Cells on Hepatic Stellate Cells by Regulating Transforming Growth Factor-ß1/Smads Signaling Pathway.

Studies have shown that human umbilical cord mesenchymal stem cells (hUCMSCs) could ameliorate liver fibrosis (LF) through inhibiting the activation of hepatic stellate cells (HSCs). However, the specific mechanisms have not been studied clearly. The purpose of this study was to explore the possible mechanism of hepatocyte growth factor (HGF)-transfected hUCMSCs in inhibiting the proliferation and activation of HSCs-T6. The upper and lower double-cell coculture system was established among HGF-hUCMSCs, LV5-NC-hUCMSCs, hUCMSCs, and HSCs-T6 in experimental groups; HSCs-T6 were cultured alone as control group. After coculturing for 1, 2, and 3 days, results showed that HGF-transfected hUCMSCs could decrease cell viability of HSCs-T6 and promote apoptosis; inhibit their activation and reduce the expression of Collagen I, Collagen III, TGF-ß1, Smad2 and Smad3, which may be related to inhibiting the activation of TGF-ß1/Smads signaling pathway. These findings suggested that HGF-transfected hUCMSCs may be used as an alternative and novel therapeutic approach for the treatment of LF.

Exogenous melatonin alleviates hemorrhagic shock­induced hepatic ischemic injury in rats by inhibiting the NF­κB/IκBα signaling pathway.

Melatonin (MT) is an indoleamine hormone that can counteract ischemia­induced organ injury through its antioxidant effects. The aim of the present study was to investigate the protective effects of exogenous MT against hemorrhagic shock (HS)­induced hepatic ischemic injury in rats, and the role of the nuclear factor (NF)­κB signaling pathway in this process. A rat model of HS­induced hepatic ischemic injury was established. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­6 and IL­1ß were measured every 6 h, and the 24­h survival rate of the rats was analyzed. All surviving rats were sacrificed after 24 h. Pathological changes in the liver and the hepatocyte apoptosis rate were observed by hematoxylin and eosin staining and TUNEL assay, respectively, and the expression levels of NF­κB p65 and NF­κB inhibitor α (IκBα) were analyzed by reverse transcription­quantitative PCR analysis and western blotting. The results demonstrated that the serum levels of ALT, AST, LDH, GDH, TNF­α, IFN­Î³, IL­6 and IL­1ß gradually increased after HS compared with those in rats subjected to a sham procedure, but this increase was attenuated by MT. Furthermore, the survival rate of the MT group was significantly higher compared with that of the HS group. The degree of pathological hepatic injury, the hepatocyte apoptosis rate, and the hepatic levels of TNF­α, IFN­Î³, IL­6 and IL­1ß were significantly decreased in the MT group compared with the HS group. In addition, the mRNA expression of NF­κB p65 was significantly decreased and the mRNA expression of IκBα was significantly increased in the MT group compared with the sham group. Furthermore, the NF­κB p65 protein levels in the MT group were significantly increased in the cytosol but decreased in the nucleus, and the IκBα protein levels were increased while those of phosphorylated IκBα were decreased compared with those in the HS group. Therefore, it may be inferred that exogenous MT alleviates HS­induced hepatic ischemic injury in rats via the inhibition of NF­κB activation and IκBα phosphorylation.

Research Progress of Mesenchymal Stem Cell Therapy for Severe COVID-19.

Corona virus disease 2019 (COVID-19) refers to a type of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Sixty million confirmed cases have been reported worldwide until November 29, 2020. Unfortunately, the novel coronavirus is extremely contagious and the mortality rate of severe and critically ill patients is high. Thus, there is no definite and effective treatment in clinical practice except for antiviral therapy and supportive therapy. Mesenchymal stem cells (MSCs) are not only characterized by low immunogenicity and homing but also have anti-inflammatory and immunomodulation characteristics. Furthermore, they can inhibit the occurrence and development of a cytokine storm, inhibit lung injury, and exert antipulmonary fibrosis and antioxidative stress, therefore MSC therapy is expected to become one of the effective therapies to treat severe COVID-19. This article will review the possible mechanisms of MSCs in the treatment of severe COVID-19.

Effect of Human Umbilical Cord Mesenchymal Stem Cells Transfected with HGF on TGF-ß1/Smad Signaling Pathway in Carbon Tetrachloride-Induced Liver Fibrosis Rats.

The research on human umbilical cord-derived mesenchymal stem cells (hUCMSCs) suggests promising therapeutic strategy for ameliorating liver fibrosis and it can be an effective alternative method of orthotopic liver transplantation. Hepatocyte growth factor (HGF) is the most basic cytokine involved in the inhibition of liver fibrosis and promotion of hepatocyte proliferation and regeneration. The objective of this study was to determine the possible mechanism about how the microencapsulated hUCMSCs made by alginate-poly-lysine-alginate (A-P-A) transfected with HGF could ameliorate liver fibrosis through the TGF-ß1/Smad signaling pathway. The microencapsulated cells were divided into four groups: hUCMSC (microcapsules of hUCMSCs), HGF (microcapsules of HGF+hUCMSCs), LV5-NC (microcapsules of LV5-NC, an rLV-EF1a-EGFP+Puro control lentiviral vector+hUCMSCs), and empty microcapsule (microcapsules without any hUCMSCs), and then transplanted by intraperitoneal injection into carbon tetrachloride (CCl4)-induced liver fibrosis rats, respectively. The results showed that the fibrosis in the hUCMSC, LV5-NC, and HGF groups was significantly alleviated. Moreover, the messenger RNA (mRNA) and protein levels of collagen I, collagen III, α-SMA, TGF-ß1, Smad2, and Smad3 were significantly decreased compared with the empty microcapsule group and these indices in HGF group were more decreased compared with hUCMSC and LV5-NC groups. This study indicated that microencapsulated hUCMSCs transfected with HGF could effectively improve CCl4-induced rat liver fibrosis and the possible mechanism was closely related to the inhibition of TGF-ß1/Smad signaling pathway.

Effect of hydrocortisone on the 28-day mortality of patients with septic acute kidney injury.

Objectives: To evaluate the efficacy of hydrocortisone in patients with septic acute kidney injury (SAKI).Methods: This retrospective cohort study consisted of all consecutive patients with SAKI who were admitted to the Taizhou First People's Hospital from March 2016 to February 2018. The patients who were treated with usual care including antibiotics, fluid resuscitation, and blood glucose control were regarded as the control group, and those received add-on hydrocortisone by the clinicians' discretion was considered in the intervention group. Hydrocortisone was administered as a 50 mg intravenous bolus every six hours for seven days. To adjust the potential baseline differences between the hydrocortisone and control groups, a 1:1 propensity score matching (PSM) was performed to identify a matched control subject for each patient in the hydrocortisone group.Results: In the propensity-matched cohort, the 28-day mortality was significantly lower for patients in the hydrocortisone group (p = .04). Both Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA) scores were significantly lower at day 7 in the hydrocortisone group (both p < .01). Serum IL-1ß, IL-6, and TNF-α concentrations significantly decreased for hydrocortisone group at day 7 (all p < .01). The levels of serum creatinine (SCr), Cystatin C (CysC), and procalcitonin (PCT) were significantly lower, while the levels of glomerular filtration rate (GFR) and urine volume were significantly higher for hydrocortisone group at day 7 (all p < .01).Conclusions: Glucocorticoid supplementation may improve renal function and reduce the 28-day mortality of patients with SAKI.

[The protective effect of bone marrow mesenchymal stem cells carrying antioxidant gene superoxide dismutase on paraquat lung injury in mice].

OBJECTIVE: To explore the possible mechanism and protective effect of BMSCs (bone mesenchymal stem cells) carrying superoxide dismutase (SOD) gene on mice with paraquat-induced acute lung injury. METHODS: To establish the cell line of BMSCs bringing SOD gene, lentiviral vector bringing SOD gene was built and co-cultured with BMSCs. A total of 100 BALB/c mice were randomly divided into five groups, namely Control group, poisoning group (PQ group) , BMSCs therapy group (BMSC group) , BMSCs-Cherry therapy group (BMSC-Cherry group) , BMSCs-SOD therapy group (BMSC-SOD group) . PQ poisoning model was produced by stomach lavaged once with 1 ml of 25 mg/kg PQ solution, and the equal volume of normal saline (NS) was given to Control group mice instead of PQ. The corresponding BMSCs therapy cell lines were delivered to mice through the tail vein of mice 4h after PQ treatment.Five mice of each group were sacrificed 3 d, 7 d, 14 d and 21 days after corresponding BMSCs therapy cell lines administration, and lung tissues of mice were taken to make sections for histological analysis. The serum levels of glutathione (GSH) , malondialdehyde (MDA) , SOD, and the levels of transforming growth factor-ß (TGF-ß) and tumor necrosis factor-α (TNF-α) in lung tissue were determined. The level of SOD was assayed by Westen-blot. RESULTS: Compared with Control group, the early (3 days) levels of SOD protein in lung tissue of PQ group obviously decreased, and the late (21 days) levels of SOD obviously increased, while in therapy groups, that was higher than that in PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) . Compared with Control group, the levels of plasma GSH and SOD of PQ group and each therapy group wae significantly lower than those in Control group, while in therapy groups, those were higher than those of PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) .Compared with Control group, the level of plasma MDA, TNF-α and TGF-ß in PQ group and therapy groups were significantly higher, while in therapy groups, that was lower than that in PQ group, and the BMSCs-SOD group showed most obvious (all P<0.05) . Lung biopsy showed that, the degree of lung tissue damage in each therapy group obviously reduced. CONCLUSION: SOD is the key factor of the removal of reactive oxygen species (ROS) in cells, that can obviously inhibit the oxidative stress damage and the apoptosis induced by PQ, thus significantly increasing alveolar epithelial cell ability to fight outside harmful environment.

[The effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat].

OBJECTIVE: To observe the effects of Nrf2 gene expression induced by RU486 at different doses on A549 cell damage induced by paraquat (PQ). METHODS: After A549 cells transfected with Ad-RUNrf2 were treated by RU486 at the doses of 10(-10), 10(-9), 10(-8) and 10(-7) mol/L for 6 h, A549 cell cultures were exposed to 10(-3) mol/L of PQ for 48 h. Then qRT-PCR and EMSA assays were used to detect the expression of Nrf2 gene, and qRT-PCR and ELISA assays were utilized to measure the effects of Nrf2 gene on the expression of the inflammatory cytokines IL-6, IL-10 and TNF-α, apoptotic factors Caspase-3, Caspase-9 and Cytochrome C. The oxidation factors (CAT and MDA protein contents) were observed by Chemical Colorimetric Analysis. RESULTS: Nrf2 gene relative expression and protein contents increased with RU486 concentrations, and the above expression was the highest when the concentration of RU486 was 10(-7) mol/L, which was significantly higher than those in control and PQ exposure groups (P < 0.01 or P < 0.05). The relative gene expression and protein expression of IL-6 and TNF-α enhanced with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05), while the change of IL-10 content was the opposite. The relative expression of Caspase3, Caspase9 and Cytochrome C genes also increased with the reduced concentrations of RU486, which were the lowest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.01 or P < 0.05). The content of CAT enhanced with RU486 concentration, which was the highest when RU486 concentration was 10(-7) mol/L, as compared with control and PQ exposure groups (P < 0.05). But the change of MDA content was the contrary. CONCLUSION: Nrf2 expression induced by RU486 can promote the balance of oxidation-antioxidation system in A549 cells and inhibit the inflammation and apoptosis factors, which has a protective effect on A549 cell injury induced by PQ.

[In vitro construction and confirmation of adenovirus containing a mifepristone (RU486)-inducible regulation system for NRF2 gene].

OBJECTIVE: To construct an adenovirus containing a mifepristone (RU486)-inducible regulation system for NRF2 gene, express the product in H460 cell and verify whether the mentioned system can control the gene expression and assess its efficiency. METHODS: A RU486-inducible regulation system for Nrf2 gene was introduced into an adenovirus. The confirmation was performed through the LUC and Dsred genes. And the expression pattern of Nrf2 at the viral level was examined by Western blot and RT-PCR (reverse transcription-polymerase chain reaction). RESULTS: The expressions of LUC and Dsred showed a rising trend with the incremental dose of RU486. After the transfection H460 cell with Ad-RUNrf2, the results of RT-PCR and Western blot demonstrated that the expression of Nrf2 was elevated with a rising dose of RU486. After the removal of RU486, the expression of Nrf2 was reduced. CONCLUSION: The construction of an adenovirus carrying Nrf2 gene regulated by a RU486-inducible system is successful, and RU486 can adjust the cellular expression of Nrf2 factor. The LUC and the Dsred expression assumes the dosage dependence along with RU486 to increase; after the Ad-RUNrf2 infects the H460 cell, through RTPCR and Western the Blot result demonstrated that the expression of Nrf2 increases along with the RU486 dosage increases, after removing RU486, the Nrf2 expression is weaken. Showing the construction of the adenovirus carrying Nrf2 gene regulated by the mifepristone (RU486)-inducible system is successful, and RU486 can adjust the Nrf2 factor in the cell the expression.

[Effect of bromoxynil on membrane potential and respiratory control rate in isolated mitochondria from mice liver and intervention effect of NAC].

OBJECTIVE: To demonstrate the effect of bromoxynil on membrane potential and respiratory control rate (RCR) in isolate mitochondria from mice liver tissue in vitro and the intervention of NAC. METHODS: The mitochondrial was randomized to control group, bromoxynil-poisoned group and NAC-protected group. S3, S4 and RCR of the mitochondria in each sample was detected by the method of oxygen electrode. Each sample was stained by JC-1 and the changes of membrane potential of mitochondria were observed under fluorescence microscope. RESULTS: The S3 [(0.031 +/- 0.008) nano atoms oxygen x mg(-1) x min(-1)], RCR (1.820 +/- 0.181) of bromoxynil-poisoned group and RCR (4.253 +/- 0.210) of NAC-protected group were significantly lower than those of control group (P<0.01); the S4 [(0.017 +/- 0.004) nano atoms oxygen x mg(-1) x min(-1)] of NAC-protected group was significantly higher than control group (P<0.01). The S3 [(0.046 +/- 0.005) nano atoms oxygen x mg(-1) x min(-1)] and RCR of NAC-protected group were significantly higher than group B (P<0.01), S4 [(0.011 +/- 0.001) nano atoms oxygen x mg(-1) x min(-1)] of NAC-protected group was significantly lower than bromoxynil-poisoned group (P< 0.01). Observation under fluorescence microscope: the red fluorescence of mitochondria was dim or disappeared in bromoxynil-poisoned group while brightened in NAC-protected group but still dimmer than control group. CONCLUSION: In vitro, the mitochondrial RCR and the mitochondrial membrane potential are decreased after the mitochondria is incubated with bromoxynil, and NAC could improve it.