Beam quality control technology for solid-state lasers based on thermal effects.

Thermal effects under high-power pumping significantly limit the laser beam quality. To address this, we developed an M2 simulation algorithm based on ray trajectory simulation and established a corresponding experimental platform. This approach optimized the M2 factor of pulsed lasers to 2.2 and output power of 25.9 W under a repetition rate of 10 kHz. The results revealed that under specific conditions, thermal effects, typically considered detrimental to beam quality, could significantly enhance it. Compared to other methods necessitating additional optical components, our strategy offers a streamlined and straightforward solution for beam quality control under high-power pumping conditions.

Acetyl-11-keto-ß-boswellic acid ameliorates renal interstitial fibrosis via Klotho/TGF-ß/Smad signalling pathway.

Acetyl-11-keto-ß-boswellic acid (AKBA), an active triterpenoid compound from the extract of Boswellia serrate, has been reported previously in our group to alleviate fibrosis in vascular remodelling. This study aimed to elucidate the in vivo and in vitro efficacy and mechanism of AKBA in renal interstitial fibrosis. The experimental renal fibrosis was produced in C57BL/6 mice via unilateral ureteral obstruction (UUO). Hypoxia-induced HK-2 cells were used to imitate the pathological process of renal fibrosis in vitro. Results showed that the treatment of AKBA significantly alleviated UUO-induced impairment of renal function and improved the renal fibrosis by decreasing the expression of TGF-ß1, α-SMA, collagen I and collagen IV in UUO kidneys. In hypoxia-induced HK-2 cells, AKBA displayed remarkable cell protective effects and anti-fibrotic properties by increasing the cell viability, decreasing the lactate dehydrogenase (LDH) release and inhibiting fibrotic factor expression. Moreover, in obstructed kidneys and HK-2 cells, AKBA markedly down-regulated the expression of TGFß-RI, TGFß-RII, phosphorylated-Smad2/3 (p-Smad2/3) and Smad4 in a dose-dependent fashion while up-regulated the expression of Klotho and Smad7 in the same manner. In addition, the effects of AKBA on the Klotho/TGF-ß/Smad signalling were reversed by transfecting with siRNA-Klotho in HK-2 cells. In conclusion, our findings provide evidence that AKBA can effectively protect kidney against interstitial fibrosis, and this renoprotective effect involves the Klotho/TGF-ß/Smad signalling pathway. Therefore, AKBA could be considered as a promising candidate drug for renal interstitial fibrosis.

Investigation into the underlying molecular mechanisms of hypertensive nephrosclerosis using bioinformatics analyses.

Hypertensive nephrosclerosis (HNS) is a major risk factor for end-stage renal disease. However, the underlying pathogenesis of HNS remains to be fully determined. The gene expression profile of GSE20602, which consists of 14 glomeruli samples from patients with HNS and 4 normal glomeruli control samples, was obtained from the Gene Expression Omnibus database. Gene ontology (GO) and pathway enrichment analyses were performed in order to investigate the functions and pathways of differentially expressed genes (DEGs). Pathway relation and co­expression networks were constructed in order to identify key genes and signaling pathways involved in HNS. In total, 483 DEGs were identified to be associated with HNS, including 302 upregulated genes and 181 downregulated genes. Furthermore, GO analysis revealed that DEGs were significantly enriched in the small molecule metabolic process. In addition, pathway analysis also revealed that DEGs were predominantly involved in metabolic pathways. The tricarboxylic acid (TCA) cycle was identified as the hub pathway in the pathway relation network, whereas the sorbitol dehydrogenase (SORD) and cubulin (CUBN) genes were revealed to be the hub genes in the co­expression network. The present study revealed that the SORD, CUBN and albumin genes as well as the TCA cycle and metabolic pathways are involved in the pathogenesis of HNS. The results of the present study may contribute to the determination of the molecular mechanisms underlying HNS, and provide insight into the exploration of novel targets for the diagnosis and treatment of HNS.

Gastroprotective effects of chebulagic acid against ethanol-induced gastric injury in rats.

Gastric ulcer is a major complication of gastrointestinal disease. This study focuses on the gastroprotection and potential mechanism of chebulagic acid (CA) in acute gastric ulceration induced by ethanol in rats. Specifically, in animal study, gastric ulceration was induced by ethanol, morphological features of gastric tissue were observed by ulcer score, H&E, masson and CD31 staining. CA can effectively decrease gastric injury, oxidative stress and proinflammatory cytokines. In addition, significant augment of prostaglandin E2 (PGE2) and nitric oxide (NO) was observed in the gastric tissues pretreated by CA. And CA prevented microcirculatory damage, aroused reparation of vascular architecture, and promoted collagen production, in associated with upregulated expressions of MMP-2, membrane type (MT) 1-MMP, VEGF, and transforming growth factor (TGF)-ß. Taken together, these results indicated that CA had a considerable gastroprotective effect on ethanol-induced gastric injury. The underlying mechanism may be ascribed to the improvement of anti-oxidant and anti-inflammatory status as well as accelerating angiogenesis.

Identification of genes and pathways potentially related to PHF20 by gene expression profile analysis of glioblastoma U87 cell line.

BACKGROUND: Glioblastoma is the most common and aggressive brain tumor associated with a poor prognosis. Plant homeodomain finger protein 20 (PHF20) is highly expressed in primary human gliomas and its expression is associated with tumor grade. However, the molecular mechanism by which PHF20 regulates glioblastoma remains poorly understood. METHODS: Genome wide gene expression analysis was performed to identify differentially expressed genes (DEGs) in U87 cells with PHF20 gene knockdown. Gene ontology (GO) and pathway enrichment analyses were performed to investigate the functions and pathways of DEGs. Pathway-net and signal-net analyses were conducted to identify the key genes and pathways related to PHF20. RESULTS: Expression of 540 genes, including FEN1 and CCL3, were significantly altered upon PHF20 gene silencing. GO analysis results showed that DEGs were significantly enriched in small molecule metabolic and apoptotic processes. Pathway analysis indicated that DEGs were mainly involved in cancer and metabolic pathways. The MAPK, apoptosis and p53 signaling pathways were identified as the hub pathways in the pathway network, while PLCB1, NRAS and PIK3 s were hub genes in the signaling network. CONCLUSIONS: Our findings indicated that PHF20 is a pivotal upstream regulator. It affects the occurrence and development of glioma by regulating a series of tumor-related genes, such as FEN1, CCL3, PLCB1, NRAS and PIK3s, and activation of apoptosis signaling pathways. Therefore, PHF20 might be a novel biomarker for early diagnosis, and a potential target for glioblastoma therapies.

Telmisartan improves vascular remodeling through ameliorating prooxidant and profibrotic mechanisms in hypertension via the involvement of transforming growth factor-ß1.

Vascular remodeling is a common complication and pathological basis of hypertension. Transforming growth factor­ß1 (TGF­ß1)/small mothers against decapentaplegic 3 (Smad3) is considered a potential therapeutic target for vascular remodeling in hypertension. The present study aimed to demonstrate the antifibrotic effects of telmisartan and examined the potential mechanisms associated with its prevention of vascular remodeling. Spontaneously hypertensive rats (SHRs) were treated with telmisartan (20 mg/kg), and vascular contractility, reactivity and oxidative stress were preliminarily evaluated. Vascular pathological alterations and collagen deposition were assessed using hematoxylin and eosin, and Masson staining, respectively. The profibrotic factors, TGF­ß1 and Smad3 were evaluated using immunofluorescence and immunohistochemistry. The protein levels of TGF­ß1/Smad3, phosphorylated (p­)Smad3, collagen­1 and α-smooth muscle actin in the aorta were assessed using western blot analysis. It was found that telmisartan attenuated chronic vasoconstriction and oxidative stress in the SHRs, and improved vascular reactivity. Telmisartan also restored vascular pathological alterations and decreased collagen deposition. In the vascular wall of the SHRs, telmisartan effectively decreased the protein levels of TGF­ß1/Smad3 and p­Smad3. Taken together, these findings indicated that telmisartan, with its antioxidant effect, prevented vascular remodeling in hypertension through preventing the TGF­ß1/Smad3 signaling pathway.

Metabonomic Strategy for the Evaluation of Chinese Medicine Salvia miltiorrhiza and Dalbergia odorifera Interfering with Myocardial Ischemia/Reperfusion Injury in Rats.

Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem, and SM-DOO group, n = 6. Rats were pretreated with homologous drugs for 7 days, and then subjected to 30 minutes of ischemia followed by 180 minutes of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamics, infarct area, histopathology, biochemical indicators, and Western blot analysis. Metabonomics technology was further performed to evaluate the endogenous metabolites profiling systematically. According to the results of pattern recognition analysis, a clear separation of MI/R injury in the Model group and Sham group was achieved and SM-DOO pretreatment group was located much closer to the Sham group than the Model group, which was consistent with results of biochemistry and histopathological assay. Moreover, potential biomarkers were identified to elucidate the drug mechanism of SM-DOO, which may be related with pathways of energy metabolism, especially tricarboxylic acid (TCA) cycle (citric acid) and ß-oxidation of fatty acids (3-hydroxybutyric, palmitoleic acid, heptadecanoic acid, and arachidonic acid). In addition, the protein expressions of p-AMPK and p-ACC in the SM-DOO group were significantly elevated, while the levels of carnitine palmitoyl-CoA transferase-1 (CPT-1), p-PDK, and p-PDC were dramatically reduced by SM-DOO. In conclusion, SM-DOO pretreatment could ameliorate MI/R injury by intervening with energy metabolism, especially TCA cycle and ß-oxidation of fatty acids. This work showed that the metabonomics method combinate with conventional pharmacological methods is a promising tool in the efficacy and mechanism research of traditional Chinese medicines.

Differential gene expression profiles between two subtypes of ischemic stroke with blood stasis syndromes.

Ischemic stroke is a cerebrovascular thrombotic disease with high morbidity and mortality. Qi deficiency blood stasis (QDBS) and Yin deficiency blood stasis (YDBS) are the two major subtypes of ischemic stroke according to the theories of traditional Chinese medicine. This study was conducted to distinguish these two syndromes at transcriptomics level and explore the underlying mechanisms. Male rats were randomly divided into three groups: sham group, QDBS/MCAO group and YDBS/MCAO group. Morphological changes were assessed after 24 h of reperfusion. Microarray analysis with circulating mRNA was then performed to identify differential gene expression profile, gene ontology and pathway enrichment analyses were carried out to predict the gene function, gene co-expression and pathway networks were constructed to identify the hub biomarkers, which were further validated by western blotting and Tunel staining analysis. Three subsets of dysregulated genes were acquired, including 445 QDBS-specific genes, 490 YDBS-specific genes and 1676 blood stasis common genes. Our work reveals for the first time that T cell receptor, MAPK and apoptosis pathway were identified as the hub pathways based on the pathway networks, while Nfκb1, Egfr and Casp3 were recognized as the hub genes by co-expression networks. This research helps contribute to a clearer understanding of the pathological characteristics of ischemic stroke with QDBS and YDBS syndrome, the proposed biomarkers might provide insight into the accurate diagnose and proper treatment for ischemic stroke with blood stasis syndrome.

Acetyl-11-Keto-ß-Boswellic Acid Attenuates Prooxidant and Profibrotic Mechanisms Involving Transforming Growth Factor-ß1, and Improves Vascular Remodeling in Spontaneously Hypertensive Rats.

Vascular remodeling is an important complication of hypertension with oxidative stress-related profibrotic pathways involved. The transforming growth factor ß1 (TGF-ß1) has been shown to be a potential target of vasoprotection, and has multiple roles in vascular remodeling. Acetyl-11-Keto-ß-Boswellic Acid (AKBA) is one of the active principles of Boswellic acids, and shows antioxidant activity in many diseases. The study is to determine effects of AKBA on systemic oxidative stress of hypertension and vascular remodeling. In the experiments, spontaneously hypertensive rats (SHR) were used. And in vitro, fibroblast was pretreated with AKBA before Ang II stimuli. In the results, treatment of AKBA markedly reduced oxidative stress, and decreased vascular remodeling by restoring vascular wall parameters and improving vascular reactivity. AKBA dramatically reduced TGF-ß1 and Smad3 expression, as shown in immunofluorescence and immunohistochemistry. In cultured fibroblast, AKBA decreased intracellular ROS levels. Cell viability and proliferation, as well as migration were inhibited by AKBA. Additionally, treatment of AKBA significantly decreased TGF-ß1 secretion in culture supernatant. Expression of TGF-ß1, Smad3, P-Smad3 and Smad7 were also decreased by AKBA in fibroblast. In conclusion, AKBA is able to attenuate oxidative stress and profibrotic mechanisms, and improve vascular remodeling in hypertension through TGF-ß1/Smad3 pathway.

Alpha-boswellic acid protects against ethanol-induced gastric injury in rats: involvement of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway.

OBJECTIVES: The purpose of this study was to assess the gastroprotective properties of alpha-boswellic acid (α-BA), a pentacyclic triterpene compound from extracts of Frankincense. METHODS: The gastroprotection of α-BA was assessed with ethanol-induced gastric lesions model, by histopathological assessment and measuring gastric juice acidity (pH), gastric wall mucus (GWM), prostaglandins E2 (PGE-2), membrane lipids peroxidation (MDA), superoxide dismutase (SOD) activity, catalase (CAT) activity and amount of nitric oxide (NO). The gastroprotective effects of α-BA through the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) anti-oxidative pathway were presented and measured by immunohistochemistry and Western blot. KEY FINDINGS: The results showed that α-BA reduced injuries associated with the administration of ethanol, gastric juice acidity and the formation of MDA and increased CAT activity and SOD activity and the level of NO and PGE-2 in a dose-depended manner. The expression of both Nrf2 and HO-1 was significantly increased in the group treated with 200 mg/kg α-BA, which suggested that activation of the Nrf2/HO-1 pathway might be critical in α-BA's prevention of gastric ulcers. CONCLUSIONS: These findings demonstrate that α-BA decreases oxidative stress and that the Nrf2/HO-1 pathway might play a role in the gastroprotective action of α-BA in ethanol-induced gastric injury in rats.