Protective effect of ginsenoside Rd against isoproterenolinduced myocardial infarction in Wistar rats

Purpose: To investigate the protective effect of ginsenoside Rd (GRd) against isoproterenol (ISO)- induced myocardial infarction in a rat model.Methods: Forty healthy male rats were equally divided into four groups (10/group). Rats in the control group received only saline, whereas rats in GRd group were intraperitoneally (i.p.) injected GRd at a dose of 50 mg/kg body weight (b.wt.) for 14 days. The other two groups were ISO-treated rats. One group (MI model) received ISO at a dose of 80 mg/kg b.wt i.p. for 2 days, while the other group (GRd + ISO group) was pretreated with GRd at a dose of 50 mg/kg for 14 days prior i.p. administration of the same dose of ISO.Results: Treatment with GRd (for 14 days) prior to ISO exposure resulted in significant increase in the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as significant decreases in heart-to-body weight ratio, infarct size, inflammatory markers {tumour nectosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6)}, relative to ISO-treated rats (p > 0.05). In addition, prior exposure to ISO led to significant elevation in malondialdehyde (MDA), cardiac troponin T (cTnT), creatine kinase (CPK), lactate dehydrogenase (LDH) and apoptotic markers (caspase-3 and caspase-9). However, pre-treatment with GRd reversed the ISO-induced histopathological changes (necrosis/oedema and altered cardiac fibres) in cardiac tissue.Conclusion: These results demonstrate that GRd ameliorates ISO-induced cardiotoxicity in rats via upregulation of the activities of antioxidants, and suppression of inflammatory and apoptotic biomarkers. Thus, GRd has cardio-protective properties.Keywords: Ginsenoside Rd, Myocardial infarction, Apoptosis, Inflammation, Antioxidant

Effect of combined vitamin D and microwave ablation of parathyroid glands on blood pressure and cardiac function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism

Purpose: To investigate the effect of microwave ablation of parathyroid glands in combination with active vitamin D on blood pressure and cardiac function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism. Methods: One hundred and twenty maintenance-hemodialysis patients with uremic secondary hyperparathyroidism admitted to Meizhou People’s Hospital were assigned to 2 groups (A and B) in the order of their admission. Each group had 60 patients. Both groups were treated with active vitamin D, while patients in group A were, in addition, subjected to microwave ablation of parathyroid glands. Blood pressure, and indices for cardiac function, thyroid function s and anemia were determined. Results: After treatment, the blood pressure of group A was significantly lower than that of group B (p < 0.05). Moreover, after treatment, there were significant improvements in indices of cardiac function, thyroid function and anemia in group A patients, relative to group B patients. Conclusion: Microwave ablation of parathyroid glands, when combined with active vitamin D, improves blood pressure, cardiac function and anemia status. Furthermore, the combined therapy enhances recovery of thyroid function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism. However, the combined therapy should be subjected to further clinical trials prior to application in clinical practice. Keywords: Microwave ablation; Parathyroid glands; Active vitamin D; Hyperparathyroidis

Efficacy and safety of tetramethylpyrazine phosphate on pulmonary hypertension: study protocol for a randomized controlled study

Background: Tetramethylpyrazine (TMP), an active ingredient in the traditional Chinese herbal medicine Rhizoma Chuanxiong, has been used clinically for the prevention and treatment of cardiovascular disease. The benefits of TMP are largely attributed to its anti-oxidative and vasodilative properties. However, the efficacy of TMP in the treatment of pulmonary hypertension (PH) is unknown. We hypothesized that TMP may have a therapeutic effect in patients with PH. Methods/design: A randomized, single-blinded, clinical study with a TMP treatment group and a control group will be conducted to evaluate the efficacy and safety of TMP intervention in patients with PH. The recruitment target is 120 subjects meeting the following criteria: (i) at rest and at sea level, mean pulmonary artery pressure above 20 mmHg and pulmonary capillary wedge pressure below 15 mmHg; (ii) type 1 or 4 PH in the stable phase; (iii) age 15-70 years; (iv) 6-min walk distance between 100 and 450 m; (v) World Health Organization (WHO) functional classification of pulmonary hypertension of II, III, or IV. Subjects will be assigned randomly into two groups at a ratio of 1:2 (control:TMP). Both groups will receive routine treatment, and the treatment group will also receive oral TMP (100 mg) three times a day for 16 weeks. All patients will be followed up for 4, 8, 12, and 16 weeks; symptoms and patient compliance will be recorded. Discussion: We aimed to determine the efficacy and safety of TMP for the treatment of PH.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Variations in growth traits and wood physicochemical properties among Pinus koraiensis families in Northeast China

This study aimed to explore and improve the different economic values of Pinus koraiensis (Siebold and Zucc.) by examining the variations in 6 growth traits and 9 physicochemical wood properties among 53 P. koraiensis half-sib families. Growth traits assessed included height, diameter at breast height, volume, degree of stem straightness, stem form, and branch number per node, while wood properties assessed included density, fiber length and width, fiber length to width ratio, and cellulose, hemicellulose, holocellulose, lignin, and ash contents. Except for degree of stem straightness and branch number per node, all other traits exhibited highly significant variations (P < 0.01) among families. The coefficients of variation ranged from 5.3 (stem form) to 66.7% (ash content), whereas, the heritability ranged from 0.136 (degree of stem straightness) to 0.962 (ash content). Significant correlations were observed among growth traits and wood physicochemical properties. Principal component analysis identified four distinct groups representing growth traits, wood chemical and physical properties, and stem form traits. Multi-trait comprehensive evaluation identified three groups of elite families based on breeding objectives, including rapid growth, improved timber production for building and furniture materials, and pulpwood production. These specific families should be used to establish new plantations

Leucine Carboxyl Methyltransferase Downregulation and Protein Phosphatase Methylesterase Upregulation Contribute Toward the Inhibition of Protein Phosphatase 2A by α-Synuclein

The pathology of Parkinson’s disease (PD) is characterized by intracellular neurofibrillary tangles of phosphorylated α-synuclein (α-syn). Protein phosphatase 2A (PP2A) is responsible for α-syn dephosphorylation. Previous work has demonstrated that α-syn can regulate PP2A activity. However, the mechanisms underlying α-syn regulation of PP2A activity are not well understood. In this study, we found that α-syn overexpression induced increased α-syn phosphorylation at serine 129 (Ser129), and PP2A inhibition, in vitro and in vivo. α-syn overexpression resulted in PP2A demethylation. This demethylation was mediated via downregulated leucine carboxyl methyltransferase (LCMT-1) expression, and upregulated protein phosphatase methylesterase (PME-1) expression. Furthermore, LCMT-1 overexpression, or PME-1 inhibition, reversed α-syn-induced increases in α-syn phosphorylation and apoptosis. In addition to post-translational modifications of the catalytic subunit, regulatory subunits are involved in the regulation of PP2A activity. We found that the levels of regulatory subunits which belong to the PPP2R2 subfamily, not the PPP2R5 subfamily, were downregulated in the examined brain regions of transgenic mice. Our work identifies a novel mechanism to explain how α-syn regulates PP2A activity, and provides the optimization of PP2A methylation as a new target for PD treatment

Identification of the Conformational transition pathway in PIP2 Opening Kir Channels

The gating of Kir channels depends critically on phosphatidylinositol 4,5-bisphosphate (PIP2), but the detailed mechanism by which PIP2 regulates Kir channels remains obscure. Here, we performed a series of Targeted molecular dynamics simulations on the full-length Kir2.1 channel and, for the first time, were able to achieve the transition from the closed to the open state. Our data show that with the upward motion of the cytoplasmic domain (CTD) the structure of the C-Linker changes from a loop to a helix. The twisting of the C-linker triggers the rotation of the CTD, which induces a small downward movement of the CTD and an upward motion of the slide helix toward the membrane that pulls the inner helix gate open. At the same time, the rotation of the CTD breaks the interaction between the CD- and G-loops thus releasing the G-loop. The G-loop then bounces away from the CD-loop, which leads to the opening of the G-loop gate and the full opening of the pore. We identified a series of interaction networks, between the N-terminus, CD loop, C linker and G loop one by one, which exquisitely regulates the global conformational changes during the opening of Kir channels by PIP2

Liver Tumor Screening and Diagnosis in CT with Pixel-Lesion-Patient Network

Liver tumor segmentation and classification are important tasks in computer aided diagnosis. We aim to address three problems: liver tumor screening and preliminary diagnosis in non-contrast computed tomography (CT), and differential diagnosis in dynamic contrast-enhanced CT. A novel framework named Pixel-Lesion-pAtient Network (PLAN) is proposed. It uses a mask transformer to jointly segment and classify each lesion with improved anchor queries and a foreground-enhanced sampling loss. It also has an image-wise classifier to effectively aggregate global information and predict patient-level diagnosis. A large-scale multi-phase dataset is collected containing 939 tumor patients and 810 normal subjects. 4010 tumor instances of eight types are extensively annotated. On the non-contrast tumor screening task, PLAN achieves 95% and 96% in patient-level sensitivity and specificity. On contrast-enhanced CT, our lesion-level detection precision, recall, and classification accuracy are 92%, 89%, and 86%, outperforming widely used CNN and transformers for lesion segmentation. We also conduct a reader study on a holdout set of 250 cases. PLAN is on par with a senior human radiologist, showing the clinical significance of our results.Comment: MICCAI 2023, code: https://github.com/alibaba-damo-academy/pixel-lesion-patient-networ

miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer.

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC

Povezanost polimorfizma pojedinačnog nukleotida gena ARID4A i kvalitete sperme kineskog vodenog bivola

ARID4A (AT-rich interaction domain 4A) is closely related to animal sperm quality traits. In the present study, the association between ARID4A gene polymorphisms of Chinese water buffalo (Bubalus bubalis) with sperm quality traits was examined, including ejaculate volume, sperm concentration, post-thaw sperm motility, and sperm abnormality of buffalo semen. Seven single-nucleotide polymorphisms (SNPs) of ARID4A gene were detected in 156 Chinese water buffaloes by Sanger sequencing and identifying overlap peaks. Among the SNPs, six were associated with at least one sperm quality trait. In brief, g.21192G>C, g.21285C>G, and g.21364A>G could be used as potential markers for selecting semen with low sperm abnormality, high ejaculate volume, sperm concentration, and sperm motility. Furthermore, 10 haplotypes (H1: -CTCGG, H2: GTGGCA, H3: GCGGCA, H4: GCTGCA, H5: GCTCGA, H6: GTGGGG, H7: GCTCCG, H8: -CGGGA, H9: GCGGCG, and H10: GTTGCA) were formed by the six SNPs through linkage disequilibrium analysis, and then 14 different combined haplotypes were collected. Correlation analysis showed that the combined H1H2 haplotype had the highest genotype frequency. Notably, the combined H1H2 haplotype had low sperm concentration, low sperm motility, and high sperm abnormality. The combined H2H3 haplotype could be used as a potential molecular marker for selecting semen with high sperm motility. In general, we illustrated a significant correlation between SNPs in ARID4A and sperm quality traits of Chinese water buffalo, which may be useful in the marker-assisted selection of buffalo breeding. This study was the first to analyze the genetic polymorphisms of ARID4A and association with sperm qualities of Chinese buffalo.Gen ARID4A (engl AT-rich interaction domain 4A) usko je povezan s kvalitetom sperme. U ovom je radu istraživana povezanost polimorfizma gena ARID4A u kineskih vodenih bivola (Bubalus bubalis) s kvalitetom sperme, uključujući volumen ejakulata, koncentraciju sperme, pokretljivost spermija nakon odmrzavanja i abnormalnost spermija u sjemenu bivola. U 156 kineskih vodenih bivola otkriveno je sedam polimorfizama pojedinačnog nukleotida (SNPs) gena ARID4A Sangerovim sekvenciranjem i identifikacijom preklopljenih vrhova. Među SNP-ovima njih je šest bilo povezano s barem jednim svojstvom kvalitete spermija. Ukratko, g. 21192G>C, g. 21285C>G i g. 21364A>G mogu se upotrijebiti kao potencijalni markeri za selekciju sjemena s niskom abnormalnošću spermija, većim volumenom ejakulata, većom koncentracijom i pokretljivošću spermija. Nadalje, šest SNP-ova formiralo je 10 haplotipova (H1: -CTCGG, H2: GTGGCA, H3: GCGGCA, H4: GCTGCA, H5: GCTCGA, H6: GTGGGG, H7: GCTCCG, H8: -CGGGA, H9: GCGGCG i H10: GTTGCA) analizom povezanosti nepodudarnosti te je ustanovljeno 14 različitih kombiniranih haplotipova. Analiza korelacije pokazala je da kombinirani haplotip H1H2 ima najveću učestalost. Kombinirani haplotip H1H2 imao je najmanju koncentraciju sperme, slabu pokretljivost seprmija i znatnu abnormalnost spermija. Kombinirani haplotip H2H3 može se upotrijebiti kao potencijalni molekularni marker za odabir sjemena s većom pokretljivošću. Općenito je pokazana znakovita korelacija između SNP-ova u ARID4A i kvalitete sperme kineskog vodenog bivola, što može biti korisno u selekciji bivola potpomognutoj markerima. Ovo je prvo istraživanje koje je analiziralo genske polimorfizme ARID4A i njihovu povezanost s kvalitetom sjemena kineskih vodenih bivola

Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein.

TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues, and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment