Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats / 中国结合医学杂志

OBJECTIVE@#To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats.@*METHODS@#The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored.@*RESULTS@#Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1 β and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01).@*CONCLUSIONS@#Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.

Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage / 中国结合医学杂志

OBJECTIVE@#To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH).@*METHODS@#Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in the rat brains were detected by Western blot.@*RESULTS@#Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01).@*CONCLUSION@#Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.

Baicalin Reduces Early Brain Injury after Subarachnoid Hemorrhage in Rats / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of baicalin on subarachnoid hemorrhage (SAH) in rats and explore the potential mechanisms.@*METHODS@#Sprague-Dawley rats underwent experimental SAH and received treatment with baicalin at 10 or 50 mg/kg after 2 and 12 h of SAH. Neurological scores, brain water content, Evans-blue extravasation, and levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO), and malondialdehyde (MDA) were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H: quinone oxidoreductase 1 (NQO1), matrix metalloproteinase-9 (MMP-9), aquaporin 4 (AQP4), occludin, and zonulaoccludens-1 (ZO-1) were detected in the brain by Western blot. Heme oxygenase-1 (HO-1) was detected by quantitative polymerase chain reaction, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed by enzyme-linked immunosorbent assay.@*RESULTS@#Baicalin attenuated EBI 24 h after SAH in rats (P<0.05). Baicalin elevated neurological scores, GSH-Px, SOD, and increased the expression of Nrf2, NQO1, HO-1, occludin, and ZO-1 in SAH rats (P<0.05 or P<0.01). Baicalin reduced MPO, MDA, and the expression of MMP-9, AQP4, TNF-α, and IL-1β (P<0.05 or P<0.01).@*CONCLUSION@#Baicalin reduced SAH-induced EBI, partially via activation of the Nrf2/HO-1 pathway and inhibition of MMP-9 and AQP4.

knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity

Blocking the programmed death-ligand 1 (PD-L1) on tumor cells with monoclonal antibody therapy has emerged as powerful weapon in cancer immunotherapy. However, only a minority of patients presented immune responses in clinical trials. To develop an alternative treatment method based on immune checkpoint blockade, we designed a novel and efficient CRISPR-Cas9 genome editing system delivered by cationic copolymer aPBAE to downregulate PD-L1 expression on tumor cells specifically knocking out Cyclin-dependent kinase 5 () gene . The expression of PD-L1 on tumor cells was significantly attenuated by knocking out , leading to effective tumor growth inhibition in murine melanoma and lung metastasis suppression in triple-negative breast cancer. Importantly, we demonstrated that aPBAE/Cas9-Cdk5 treatment elicited strong T cell-mediated immune responses in tumor microenvironment that the population of CD8 T cells was significantly increased while regulatory T cells (Tregs) was decreased. It may be the first case to exhibit direct PD-L1 downregulation CRISPR-Cas9 genome editing technology for cancer therapy. It will provide promising strategy for preclinical antitumor treatment through the combination of nanotechnology and genome engineering.

Propofol attenuates neuroinflammation and brain damage via modulating PI3K/Akt signaling pathway in rats of focal cerebral ischemia / 中国药理学通报

Aim To explore whether propofol attenuates neuroinflammation and brain damage via modulating PI3K/Akt signaling pathway following focal cerebral ischemia in rats, and further investigate the possible mechanisms. Methods Sprague-Dawley rats which underwent the cerebral ischemic injury by the suture occlusion model were randomly divided into sham operation, MCAO, propofol-treated and LY294002 groups. Neurological deficit scores, cerebral infarct size, and cerebral water content were measured , then the myeloperoxidase (MPO) activities in rat brain were measured as an index of neutrophil infiltration. The content of TNF-α and IL-1β in blood was determined using ELISA; the expressions of p-Akt and Akt in rat brain were detected by Western blot. Results Propofol reduced neurological deficit scores, cerebral infarct size, cerebral water content, MPO activity , TNF-α and IL-1β content, which were all abolished by LY294002. Propofol up-regulated the expression of p-Akt, which was inhibited by LY294002. Conclusion Propofol attenuates neuroinflammation and ischemic brain damage via modulating the PI3K/Akt signaling pathway.

Research progress on biological activities and synthesis of alkaloids in plants from Chimonanthus Lindl / 中草药

The plants of Chimonanthus Lindl. are endemic traditional medicinal plants in China. As the important components of these plants, the Chimonanthus alkaloids showed biological activities such as hypotensive activity, anticonvulsant, antifungal, antiviral, analgesia, antitumor, and melanogenesis inhibitory properties. In this paper, the types, bioactivities, and synthesis of alkaloids in plants of Chimonanthus Lindl. were reviewed systematically for providing reference in the further research and development of Chimonanthus alkaloids.

Renal expression of hypoxia inducible factor-1α in patients with chronic kidney disease: a clinicopathologic study from nephrectomized kidneys.

Background & objectives: Hypoxia inducible factor-1α (HIF-1α) has been shown to play a role in the pathogenesis of renal interstitial fibrosis. However, the relationship of HIF-1α expression intensity in human renal tissue with the degree of renal function or renal fibrosis has not been investigated. We therefore, undertook this study to assess the relationship between HIF-1α expression and degree of renal impairment and renal fibrosis using renal tissue from nephrectomized kidneys from patients with chronic kidney disease. Methods: This retrospective study was performed with 70 patients undergoing unilateral or bilateral nephrectomy because of renal cell carcinoma, urothelial cell carcinoma, or renal abscess. Immunohistochemical analysis of HIF-1α expression in non-tumourous or non-abscess renal parenchyma was performed. The patients were divided into two groups: group 1 (n=37) with low intensity HIF-1α expression and group 2 (n=33) with high intensity HIF-1α expression. Results: The intensity of renal HIF-1α expression was significantly associated with serum creatinine level (P=0.005), estimated glomerular filtration rate (P=0.02), fibrosis score of the interstitium (P=0.004) and glomerular sclerosis (P=0.013). A high intensity of HIF-1α expression tended to be associated with lower serum creatinine, higher estimated glomerular filtration rate, low interstitial fibrosis score and low glomerular sclerosis. In addition, multivariate analysis by step-wise logistic regression demonstrated that interstitial fibrosis was the only independent factor associated with the intensity of renal HIF-1α expression (OR 4.107, CI 1.535-11.313, P=0.005). Interpretation & conclusions: This study demonstrated a correlation between intensity of HIF-1α expression and degree of renal interstitial fibrosis. The association demonstrated an elevated HIF-1α expression in less severe kidney disease. The intensity of HIF-1α renal expression plays a role in the pathogenesis of chronic kidney disease.

Borderline clear cell adenofibroma with extensive hemorrhagic necrosis

Borderline clear cell adenofibroma of the ovary is rather rare since most of clear cell tumors are carcinomas. We report a case of ovarian borderline clear cell adenofibroma in a 52-year-old postmenopausal woman. The tumor had the characteristic histologic features of borderline clear cell adenofibroma except for central extensive hemorrhagic necrosis. The prognosis of borderline clear cell adenofibroma is excellent. Because the invasiveness cannot be assessed in the necrotic areas, our patient needed long-term follow-up

Perivascular epithelioid cell tumor [PEComa] of the uterus with aggressive behavior at presentation

Perivascular epithelioid cell tumor [PEComa] is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells [PECs]. Both benign and malignant tumors have been identified, but the criteria for diagnosis of malignancy have not been fully established due to the rarity of the tumor. We report on a case of uterine PEComa in a 33-year old woman with lymph node metastasis at presentation. The tumor had the characteristic histologic features of PEComa with cytologic atypia, mitotic activity of 2/10 high power field [HPF], and necrosis; it exhibited immunopositivity for HMB-45, calponin and desmin and was negative for melan-A. The patient received neoadjuvant chemotherapy, debulking surgery and adjuvant chemotherapy. No evidence of recurrence or metastasis was apparent 8 months after surgery