We explored the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on CCl4-induced liver fibrosis with respect to the intestinal hepatic axis using a rat model. Histopathological staining results showed that DOP alleviated extensive fibrous tissue proliferation in interstitium and lessened intestinal mucosal damage. Western blot and PCR results showed that DOP maintained intestinal balance by upregulating the expression of tight junction proteins such as occludin, claudin-1, ZO-1, and Bcl-2 proteins while downregulating the expression of Bax and caspase-3 proteins in the intestine. The transepithelial electrical resistance (TEER) value of the LPS-induced Caco-2 monolayer cell model was increased after DOP administration. These illustrated that DOP can protect the intestinal mucosal barrier function. DOP also inhibited activation of the LPS-TLR4-NF-κB signaling pathway to reduce the contents of inflammatory factors TGF-β and TNF-α, increased the expression of anti-inflammatory factor IL-10, and significantly decreased α-SMA and collagen I expression. These results indicated that DOP maintained intestinal homeostasis by enhancing tight junctions between intestinal cells and reducing apoptosis, thereby inhibiting activation of the LPS-TLR4-NF-κB signaling pathway to protect against liver fibrosis.
To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt (TmEPS) for the treatment of cavernous transformation of the portal vein (CTPV).The clinical data of 20 patients with CTPV who underwent TmEPS between December 2020 and January 2022 at Henan Provincial People's Hospital were retrospectively collected. The superior mesenteric vein (SMV) trunk was patent or partially occluded in these patients. An extrahepatic portosystemic shunt between the inferior vena cava and the SMV was established using a stent graft through an infraumbilical median longitudinal mini-laparotomy. The technical success, efficacy, and complication rates were evaluated, and the pre- and postoperative SMV pressures were compared. Patients' clinical outcomes and shunt patency were assessed.TmEPS was successfully performed in 20 patients. The initial puncture success rate of the balloon-assisted puncture technique is 95%. The mean SMV pressure decreased from 29.1 ± 2.9 mmHg to 15.6 ± 3.3 mmHg (p < 0.001). All symptoms of portal hypertension resolved. No fatal procedural complications occurred. During the follow-up period, hepatic encephalopathy occurred in two patients. The remaining patients remained asymptomatic. All shunts were patent.TmEPS is a feasible, safe, and effective treatment option for patients with CTPV.
Excess acetaminophen(APAP) can be converted by the cytochrome P450 system to the toxic metabolite N-acetyl-p-benzoquinoneimine(NAPQI), which consumes glutathione(GSH). When GSH is depleted, NAPQI covalently binds with proteins, inducing mitochondrial dysfunction and oxidative stress and thereby leading to hepatotoxicity. Schisandrin C(SinC) is a dibenzocyclooctadiene derivative isolated from Schisandra chinensis. Although there is some evidence showing that SinC has hepatoprotective activity, its protective effect and mechanism on APAP-induced liver injury remain unclear. In this paper, an acute liver injury mouse model was established by intraperitoneal injection of APAP at a dose of 400 mg·kg~(-1) to evaluate the effect of SinC administration on the APAP-induced liver injury and its mechanism through an animal experiment. At the same time, a potential candidate drug was provi-ded for traditional Chinese medicine(TCM) prevention and treatment of overdose APAP-induced liver injury. In the APAP-induced liver injury mouse model, we found that SinC can relieve hepatic histopathological lesions and significantly reduce the activities of alanine aminotransferase(ALT), aspartate aminotransferase(AST) and alkaline phosphatase(ALP). It was also capable of increasing the content of GSH and superoxide dismutase(SOD) and decreasing the levels of total bilirubin(TBIL), direct bilirubin(DBIL), malondialdehyde(MDA), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α). Further analysis showed that SinC decreased the content of CYP2 E1 in liver tissues at protein and mRNA levels and increased nuclear factor erythroid 2-related factor 2(Nrf2) and the expression of its downstream targets(including HO-1, NQO1 and GCLC). Taken together, the above results indicate that SinC can alleviate APAP-induced liver injury by reducing the expression of CYP2 E1, suppressing apoptosis, improving inflammatory response and activating the Nrf2 signaling pathway to inhibit oxidative stress.
Objective
To investigate the protective effect of oridonin on hyperoxia-induced lung injury (HALI).
Methods
A total of 46 SD rats were randomly divided into control group (n=7), HALI group (n=13), Nec-1 (necroptosis inhibitor) group (n=13), and oridonin group (n=13). Rats were exposed to pure oxygen for 6 h at 0.25 MPa to induce HALI. Then the rats were intraperitoneally injected with 1 mg/kg Nec-1 or 10 mg/kg Oridonin, 30 min before hyperoxia exposure. Rats were sacrificed at 24 or 48 h after the end of hyperoxia exposure. Lung injury was assessed by histological examination, lung wet-to-dry ratio (W/D), bronchoalveolar lavage fluid (BALF) examinations, assessments of oxidative stress and inflammatory factors in the lung; lung tissues were also collected for the detection of RIP1, RIP3, and MLKL protein expressions by Western blotting and evaluation of the interaction between RIP1 and RIP3.
Results
As compared with the control group, hyperoxia exposure resulted in significant lung injury and increase in the number of necroptosis positive cells, which were accompanied by the elevated expressions of RIP1, RIP3 and MLKL in the lung. As compared with the HILI group, intraperitoneal injection of oridonin could improve lung injury to a certain extent, inhibit oxidative stress and inflammatory factors, reduce the necroptosis positive cells [HALI group: 64.7±6.5 (RIP1), 46.3±5.4 (RIP3); Nec-1 group: 39.4±4.8, 26.6±4.0; Oridonin group: 36.9±5.4, 27.1±3.9], decrease the expressions of RIP1, RIP3, and MLKL, and down-regulate the interaction between RIP1 and RIP3.
Conclusion
This study indicates that the lung protective effect of oridonin on HALI may be related to its inhibitory effect on necroptosis in the lung.
Key words:
Hyperoxia induced lung injury; Necroptosis; Oridonin; Lung protection; Rat
Abstract Evidence has shown a strong relationship between smoking and epithelial mesenchymal transition (EMT). α5‐nicotinic acetylcholine receptor (α5‐nAChR) contributes to nicotine‐induced lung cancer cell EMT. The cytoskeleton‐associated protein PLEK2 is mainly involved in cytoskeletal protein recombination and cell stretch migration regulation, which is closely related to EMT. However, little is known about the link between nicotine/α5‐nAChR and PLEK2 in lung adenocarcinoma (LUAD). Here, we identified a link between α5‐nAChR and PLEK2 in LUAD. α5‐nAChR expression was correlated with PLEK2 expression, smoking status and lower survival in vivo. α5‐nAChR mediated nicotine‐induced PLEK2 expression via STAT3. α5‐nAChR/PLEK2 signaling is involved in LUAD cell migration, invasion and stemness. Moreover, PLEK2 was found to interact with CFL1 in nicotine‐induced EMT in LUAD cells. Furthermore, the functional link among α5‐nAChR, PLEK2 and CFL1 was confirmed in mouse xenograft tissues and human LUAD tissues. These findings reveal a novel α5‐nAChR/PLEK2/CFL1 pathway involved in nicotine‐induced LUAD progression.
Objective To explore the effects of recombinant plasmids of pGPU6/GFP/NeoshRNA-CTGF (shRNA-CTGF) on the type Ⅰ collagen (COL-Ⅰ) protein expression in keloid,through RNA interference on connective tissue growth factor (CTGF) in vivo and in vitro.Methods Recombinant plasmids were designed and constructed by specific shRNA-CTGF; After transfeced human keloid fibroblast with shRNA-CTGF in vitro,RT-PCR was used to detect the CTGF mRNA level,and Western blot to detect the secretion of COL-Ⅰ.After transfected the keloid of nude mice with shRNA-CTGF in vivo,RT-PCR was used to detect the CTGF and COL-Ⅰ mRNA level,and Western blot was used to detect the protein expression of COL-Ⅰ.Results Recombinant plasmids of CTGF were successfully constructed,and the CTGF gene expression was significantly decreased in vivo and in vitro by 86.8％ and 54.1 ％,respectively; Down-regulation of CTGF in vitro significantly inhibited the mRNA and protein level of COL-Ⅰ by 76.8％ and 65.6％,respectively; Down-regulation of CTGF in vivo significantly reduced the COL-Ⅰ mRNA and protein level by 52.7％ and 48.0％,respectively.Conclusions CTGF gene expression is successfully down-regulated by the recombinant plasmid of shRNA-CTGF in vivo and in vitro.shRNA-CTGF significantly reduces the COL-Ⅰ protein level in keloid.It implies that CTGF gene is a potential target in the therapy of pathological scar.
Key words:
Keloid; Connective tissue growth factor (CTGF) ; Fibroblast; RNA interference (RNAi)
Background and objectivesRadiation injury poses a serious threat to human health, causing complex and multifaceted damage to cells and tissues. Such injury can be caused by various factors, including nuclear accidents, medical radiation therapy, and space travel. Currently, finding effective treatment methods and drugs to mitigate the harmful effects of radiation injury on the human body is a crucial research direction. This study aimed to explore the protective effects and mechanisms of Licochalcone B (Lico B) on radiation-induced cell damage and radiation-induced mortality in mice.
Objective To approach the mechanism and efficacy of regional intra-arterial infusion chemotherapy with the mixture of lipid emulsion-CDDP (LE-CDDP) for treatment of locally advanced pancreatic cancer. Methods Twenty-four health dogs were divided into four groups (group A, B, C, and D). The dosage of CDDP was used in 4 mg/kg/body weight for each animal The 20% LE, as a solvent, was used in the experimental animals with 2 ml/kg/ body weight (group A) and 1 ml/kg/bedy weight (group B), respectively. Normal sodium (NS) as a solvent was used as control with 2 ml/kg/bedy weight (group C) and 1 ml/kg/body weight (group D), respectively. The LE-CDDP mixture and the NS-CDDP mixture were infused into the proximal segment of splenic artery under the DSA, with transfemoral arterial approach. Blood samples were collected after infusion at 0,3,5,10,20,30,40,50,60 min and the tissues were obtained after the 60 min's blood sample was collected. Blood samples, absorbent gland in peripancreas, liver, spleen, kidney, heart, portal vein, the superior segment of jejunal and pancreas and parapancreatic tissues were obtained for CDDP concentration analysis and histopatholngic examination. Results The values of the area under curve (AUC), the incipient serum concentration ( C0 ) and the elimination half-life (t1/2 ) of the serum CDDP concentration-time curve in four groups were A (54. 5 ± 10.1)%,(2.6±0.5) mg/L, (16.7±3.6) min;B (18.3±6.0)%,(1.5±0.2) mg/L, (47.9 ± 11.1) min; C (116.7±20.6)%, (6.5±0.4) mg/L, (10.5±2.8) min and D (126.6±30.7)%, (5.5±0.4) mg/L, ( 10. 1±3. 1 ) min, respectively. There were significant difference among these four groups ( F(AUC) = 42. 42, F(C0) = 249. 61, F( t1/2 ) = 12. 48, P 0. 05 ). Perivascular lymphocytic and neutrophilic infiltration, congestion and hemorrhage were found in the pancreas, parapancreatic absorbent gland, liver and spleen in the group A and group B. The micro-particles of intralipid were present in the capillary vessel of these tissues. No specific pathological changes were found in other groups and organs. Conclusions The regional intra-arterial infusion with LE-CDDP mixture could increase the pancreatic CDDP concentration, meanwhile, it also could decrease the serum CDDP concentration. The more of the CDDP concentration in the LE-CDDP mixture, the more CDDP concentration at the pancreatic tissue accordingly.
Key words:
Pancreatic neoplasms; Fat emulsions, intravenous; Cisplatin; Radiography, interventional; Animal experimentation
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)