DEAD-Box Helicase 17 circRNA (circDDX17) Reduces Sorafenib Resistance and Tumorigenesis in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver malignancy. Despite significant progress in HCC treatment, resistance to chemotherapy and tumor metastasis are the main reasons for the unsatisfactory prognosis of HCC. Circular RNAs (circRNAs) have been extensively documented to play a role in the development of various types of cancer. AIMS: Here, we investigated the role of DEAD-box helicase 17 circRNA (circDDX17) in HCC and its underlying molecular mechanisms. METHODS: Our research employed various techniques including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8), flow cytometry, dual luciferase reporter assay, RNA immunoprecipitation (RIP), and western blot analysis. Additionally, we conducted a tumor xenograft assay to investigate the in vivo function of circDDX17. RESULTS: Firstly, the expression of circDDX17 was downregulated in HCC tissues and cells. Through functional experiments, it was observed that the overexpression of circDDX17 enhanced the sensitivity of sorafenib, promoted apoptosis, and inhibited the process of epithelial-mesenchymal transition (EMT) in vitro. Additionally, in vivo studies revealed that circDDX17 reduced tumor growth and increased sorafenib sensitivity. Mechanically, circDDX17 competitively combined miR-21-5p to suppress PTEN expression and activate the PI3K/AKT pathway. Furthermore, our rescue assays demonstrated that circDDX17 act as a tumor suppressor by blocking sorafenib resistance and tumorigenesis, while the inhibitory effect caused by circDDX17 upregulation was neutralized when miR-21-5p was overexpressed, PTEN was silenced, or the PI3K/AKT pathway was activated. CONCLUSION: Our findings firstly confirmed that circDDX17 suppressed sorafenib resistance and HCC progression by regulating miR-21-5p/PTEN/PI3K/AKT pathway, which may provide novel biomarkers for the diagnosis, treatment and prognosis of HCC.

Combined gas well hydrate prevention and control technology and its application.

The high pressure in some gas wells, such as those in the Xushen gas field in Daqing, China, makes them susceptible to freezing and hydrate blockages. Downhole throttling technology is widely used to reduce costs during well construction, however, due to the limitations of temperature, pressure and depth structure, this technology is sometime applied independently in some gas wells in which freezing and blockages are a frequent problem that can seriously affect production capacity. Moreover, artificial alcohol injection of 'passive plugging' to prevent hydrate formation not only consumes significant amounts of methanol but its efficiency is also dependent on factors such as weather, personnel and equipment, so it is not a continuous solution. In order to solve the above problems, the mechanism of hydrate formation was analyzed in this study, from which a combined mechanical and chemical hydrate control process was developed. OLGA software was used to design the process parameters of the novel mechanical and chemical inhibition technology for hydrate prevention and control, and also to simulate and analyze the wellhead temperature, pressure and hydrate generation once the process was implemented. Based on the results of the parameters calculation, the downhole throttle and hydrate inhibitor automatic filling device are used to realize the functions of downhole throttle depressurization and hydrate inhibitor continuous filling, reduce the wellhead pressure and hydrate generation temperature, and ensure the continuous production of gas well. This novel combination process was subsequently tested in three wells in the Daqing gas oilfield. Measurements showed that the average daily gas increase from a single well was 0.5×104m3, methanol consumption was reduced from the original maximum daily amount of 1750 kg to just 60 kg, the manual maintenance workload was reduced by 80%, and the rate of the well openings was increased from 45% to 100%. These results proved that this technology is feasible and efficient for applications in gas wells with high downhole pressure and low wellhead temperature, and, thus, provides important technical support for the prevention of gas hydrate and improvement of gas well production.

Potential Role of Intrapulmonary Concomitant Lesions in Differentiating Non-Neoplastic and Neoplastic Ground Glass Nodules.

Purpose: To determine the value of intrapulmonary concomitant lesions in differentiating non-neoplastic and neoplastic ground-glass nodules (GGNs). Patients and Methods: From January 2014 to March 2022, 395 and 583 patients with confirmed non-neoplastic and neoplastic GGNs were retrospectively enrolled. Their clinical and chest CT data were evaluated. The CT features of target GGNs and intrapulmonary concomitant lesions in these two groups were analyzed and compared, and the role of intrapulmonary concomitant lesions in improving differentiation was evaluated. Results: The intrapulmonary concomitant lesions were more common in patients with non-neoplastic GGNs than in those with neoplastic ones (87.88% vs 82.18%, P = 0.015). Specifically, patients with non-neoplastic GGNs had a higher incidence of multiple solid nodules (SNs), patchy ground-glass opacity/consolidation, and fibrosis/calcification in any lung fields (each P < 0.05). Logistic regression analysis indicated that patients < 44 years old, diameter < 7.35 mm, irregular shape, and coarse margin or ill-defined boundary for target GGN, pleural thickening, and concomitant SNs in the same lobe and fibrosis or calcification in any lung field were independent indicators for predicting non-neoplastic GGNs. The AUC of the model for predicting non-neoplastic GGNs increased from 0.894 to 0.926 (sensitivity, 83.10%; specificity, 87.10%) after including the concomitant lesions in the patients' clinical characteristics and CT features of target GGNs (P < 0.0001). Conclusion: Besides the patients' clinical characteristics and CT features of target GGNs, the concomitant multiple SNs in the same lobe and fibrosis/calcification in any lung field should be considered in further differentiating non-neoplastic and neoplastic GGNs.

Significance of marginal vessels in differentiating peripheral small-cell lung cancer and benign lung tumor.

BACKGROUND: Some peripheral small cell lung cancers (pSCLCs) and benign lung tumors (pBLTs) have similar morphological features but different treatment and prognosis. PURPOSE: To determine the significance of marginal vessels in differentiating pSCLCs and pBLTs. MATERIAL AND METHODS: A total of 57 and 95 patients with pathological confirmed nodular (≤3 cm) pSCLC and pBLT with similar morphological features were enrolled in this study retrospectively. The patients' clinical characteristics and computed tomography (CT) features of tumors and marginal vessels (vessels connecting with tumors) were analyzed and compared. RESULTS: Compared with pBLTs, pSCLCs had a larger diameter (P = 0.001) but lower enhancement (P = 0.015) and fewer had calcification (P = 0.013). Compared with pBLTs, more lesions had proximal (70.2% vs. 22.1%) and distal (59.6% vs. 4.2%) marginal vessels in pSCLCs (each P < 0.0001). In addition, in pSCLCs, the numbers of proximal (1.3 ± 1.4 vs. 0.3 ± 0.6), distal (2.4 ± 3.1 vs. 0.1 ± 0.5), and total (3.6 ± 3.5 vs. 0.4 ± 1.0) marginal vessels were all more than those in pBLTs (each P < 0.001). Receiver operating characteristic curve analysis revealed the positive distal marginal vessel sign had the highest specificity (95.8%), and the number of total marginal vessels had the best performance in discriminating pSCLC from pBLT (cutoff value = 1.5, AUC = 0.80, 95% CI = 0.72-0.89, sensitivity = 70.2%, and specificity = 91.6%). CONCLUSION: For peripheral solid nodules similar to pBLTs but without any calcification, the possibility of pSCLC should be considered if they have multiple marginal vessels (≥2), especially the distal ones.

The emerging potential role of p62 in cancer treatment by regulating metabolism.

p62 is an important multifunctional adaptor protein participating in autophagy and many other activities. Many studies have revealed that p62 is highly expressed in multiple cancers and decreasing its level can effectively lower the proliferation ability of cancer cells. Moreover, much research has highlighted the significant role of the regulation of cancer cell metabolism in helping to treat tumors. Recent reports demonstrate that p62 could regulate cancer cell metabolism through various mechanisms. However, the relationship between p62 and cancer cell metabolism as well as the related mechanisms has not been fully elucidated. In this review, we describe glucose, glutamine, and fatty acid metabolism in tumor cells and some signaling pathways that can regulate cancer metabolism and are mediated by p62.

Natural Flavonoids and Ferroptosis: Potential Therapeutic Opportunities for Human Diseases.

Flavonoids are a class of bioactive phytochemicals containing a core 2-phenylchromone skeleton and are widely found in fruits, vegetables, and herbs. Such natural compounds have gained significant attention due to their various health benefits. Ferroptosis is a recently discovered unique iron-dependent mode of cell death. Unlike traditional regulated cell death (RCD), ferroptosis is associated with excessive lipid peroxidation on cellular membranes. Accumulating evidence suggests that this form of RCD is involved in a variety of physiological and pathological processes. Notably, multiple flavonoids have been shown to be effective in preventing and treating diverse human diseases by regulating ferroptosis. In this review, we introduce the key molecular mechanisms of ferroptosis, including iron metabolism, lipid metabolism, and several major antioxidant systems. Additionally, we summarize the promising flavonoids targeting ferroptosis, which provides novel ideas for the management of diseases such as cancer, acute liver injury, neurodegenerative diseases, and ischemia/reperfusion (I/R) injury.

Clinical and Computed Tomography Characteristics for Early Diagnosis of Peripheral Small-cell Lung Cancer.

PURPOSE: To investigate the clinical and computed tomography (CT) characteristics of peripheral small-cell lung cancer (pSCLC) to improve its early diagnosis. PATIENTS AND METHODS: In total, 70, 132, 69, and 95 patients with pathological confirmed nodular (≤3 cm) pSCLC, peripheral non-small cell lung cancer (pNSCLC), benign lung tumor (pBLT), and inflammatory lesion (pIL) were enrolled in this study retrospectively. The clinical and CT data of studied patients with different lesions were analyzed and compared by univariate analysis. Multivariate analysis was used to reveal the key features to distinguish pSCLC from pNSCLC, pBLT, and pIL, respectively. RESULTS: Univariate and multivariate analysis of the clinical and CT characteristics of studied patients indicated that 1) compared with pNSCLC and pIL, vessel convergence, spiculation, and peripheral ground-glass opacity were less common in pSCLC; 2) density homogeneity (OR = 38.84-120.21, P < 0.05), bronchial cutoff sign (OR = 10.00-60.13, P = 0.001), hilar lymph node enlargement (OR = 22.81-95.08, P < 0.0001) (pSCLC vs pNSCLC, pBLT, and pIL), male sex (OR = 5.53-10.92, P < 0.05) (pSCLC vs pNSCLC and pBLT), and emphysema (OR = 36.57-56.63, P < 0.05) (pSCLC vs pBLT and pIL) were significantly and independently associated with pSCLC. Type I and II bronchial cutoff sign, especially type I, were closely related to pSCLC. CONCLUSION: Peripheral solid nodules with homogeneous density, bronchial cutoff sign, hilar lymph node enlargement, but without spiculation or vessel convergence in male patients with emphysema should be highly suspected of pSCLC.

[Mechanism and experimental verification of Dachengqi Decoction in treatment of sepsis based on network pharmacology].

This study aims to predict the material basis and mechanism of Dachengqi Decoction in the treatment of sepsis based on network pharmacology. The chemical constituents and targets of Dachengqi Decoction were retrieved from TCMSP, UniPot and DrugBank and the targets for the treatment of sepsis from OMIM and GeneCards. The potential targets of Dachengqi Decoction for the treatment of sepsis were screened by OmicShare. STRING database and Cytoscape 3.7.2 were used to construct the Chinese medicinal-active component-target-disease, active component-key target-key pathway, and protein-protein interaction(PPT) networks. The gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID(P<0.05). Finally, the animal experiment was conducted to verify some targets and pathways. A total of 40 active components and 157 targets of the Dachengqi Decoction, 2 407 targets for the treatment of sepsis, and 91 common targets of the prescription and the disease were also obtained. The key targets were prostaglandin G/H synthase 2(PTGS2), prostaglandin G/H synthase 1(PTGS1), protein kinase cAMP-dependent catalytic-α(PRKACA), coagulation factor 2 receptor(F2 R), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic gamma subunit(PIK3 CG), dipeptidyl peptidase 4(DPP4), etc. A total of 533 terms and 125 pathways were obtained for the 91 targets. The main terms were the response to drug, negative regulation of apoptotic process, positive regulation of nitric oxide biosynthetic process and lipopolysaccharide-mediated signaling pathway, and the pathways included pathways in cancer, hepatitis B, and phosphatidylinositol 3-kinase and protein kinase B(PI3 K/Akt) signaling pathway. The animal experiment confirmed that Dachengqi Decoction can down-regulate inflammatory cytokines interleukin-1ß(IL-1ß), IL-6 and tumor necrosis factor α(TNF-α)(P<0.01). It could also reduce the wet/dry weight ratio of lung tissue, the level of myeloperoxidase(MPO) and the phosphorylation of PI3 K and Akt(P<0.01). These results indicated that Dchengqi Decoction could act on inflammation-related targets and improve sepsis by inhibiting PI3 K/Akt signaling pathway. The animal experiment supported the predictions of network pharmacology. Dachengqi Decoction intervenes sepsis via multiple components, multiple targets, and multiple pathways. The result lays a foundation for further research on the mechanism of Dachengqi Decoction in the treatment of sepsis.

A carbazole functionalized semiconducting compound as a heavy atom free photosensitizer for phototherapy against lung cancer.

Semiconducting compounds with high photostability and excellent photothermal ability are potential candidates for phototheranostics. In this paper, the heavy atom free compound 3,6-bis(5-(4-(9H-carbazol-9-yl)phenyl)furan-2-yl)-2,5-bis(2-octyldodecyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (denoted as DPPCz) has been designed and synthesized through a C-H activation coupling reaction. DPPCz has a high singlet oxygen quantum yield (1O2 QY) of 40.3% in DCM. In addition, DPPCz NPs obtained by nanoprecipitation exhibit a high photothermal conversion efficiency (48.2%) in water. DPPCz NPs have a low half inhibitory concentration (IC50) of 7.1 µg mL-1 towards human lung cancer cells (A549) with irradiation while the dark toxicity is almost negligible even at high concentrations. Furthermore, in vivo photothermal imaging guided study demonstrates that these NPs are able to inhibit tumor growth with the help of laser. The H&E stained pictures of the normal tissues indicate the biosafety of DPPCz NPs in that no obvious damage was observed. Our results demonstrate that DPPCz NPs are potential semiconducting photosensitizers for phototheranostics.

Two Ru(II) compounds with aggregation induced emission as promising photosensitizers for photodynamic therapy.

Design and preparation of photosensitizers (PSs) play an important role in photodynamic therapy (PDT). PDT mainly relies on the production of toxic reactive oxygen species (ROS) of the PSs. Conventional fluorophores, however, often suffer from aggregation caused quenching (ACQ), which limits the potential of PSs as fluorescent imaging agents. Molecules with aggregation-induced emission (AIE) properties maintain high fluorescence and dispersity in aqueous solutions, overcoming the ACQ effect. Ruthenium (II)-based AIE compounds are highly biocompatible molecules and can be used for response cell imaging. In the current study, two novel Ru(II)-based AIE compounds with main ligands 1,3-di(2H-tetrazol-5-yl)benzene (Hphbtz) by changing auxiliary ligand 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) have been successfully synthesized and characterized, [Ru(Hphbtz)(bipy)2][PF6] (1) and [Ru(Hphbtz)(phen)2][PF6] (2). The NPs show strong intra-cellular fluorescence and also simultaneously exhibited potent cytotoxic activity. These compounds can self-assemble to form nanoparticles (NPs) by nanoprecipitation. The compounds are found to exhibit a high AIE property with emission maxima at 353 nm and 380 nm, respectively. And the compounds have the low IC50 (half maximal inhibitory concentration) of only 15 µg/mL (1.94 µM) and 13 µg/mL (1.58 µM) on HeLa cells, respectively. Meanwhile, negligible dark toxicity has been also observed for these NPs. The results show that [Ru(Hphbtz)(bipy)2][PF6] (1) and [Ru(Hphbtz)(phen)2][PF6] (2) NPs can inhibit cell proliferation in vitro, and may be potential candidates for photodynamic therapy.

Phytochemistry and Pharmacological Activities of Wolfiporia cocos (F.A. Wolf) Ryvarden & Gilb.

Poria cocos is the dried sclerotium of Wolfiporia cocos (F.A. Wolf) Ryvarden & Gilb., which was the current accepted name and was formerly known as Macrohyporia cocos (Schwein.) I. Johans. & Ryvarden, Pachyma cocos (Schwein.) Fr., Poria cocos F.A. Wolf and Sclerotium cocos Schwein. It is one of the most important crude drugs in traditional Chinese medicine, with a wide range of applications in ameliorating phlegm and edema, relieving nephrosis and chronic gastritis and improving uneasiness of minds. Its extensive pharmacological effects have attracted considerable attention in recent years. However, there is no systematic review focusing on the chemical compounds and pharmacological activities of Poria cocos. Therefore, this review aimed to provide the latest information on the chemical compounds and pharmacological effects of Poria cocos, exploring the therapeutic potential of these compounds. We obtained the information of Poria cocos from electronic databases such as SCI finder, PubMed, Web of Science, CNKI, WanFang DATA and Google Scholar. Up to now, two main active ingredients, triterpenes and polysaccharides of Poria cocos, have been identified from Poria cocos. It has been reported that they have pharmacological effects on anti-tumor, anti-bacterial, anti-oxidant, anti-inflammatory, immunomodulation, and liver and kidney protection. The review summarizes the phytochemistry and pharmacological properties of Poria cocos, which suggest that researchers should focus on the development of new drugs about Poria cocos to make them exert greater therapeutic potential.

Boosting type I process of Ru(II) compounds by changing tetrazole ligand for enhanced photodynamic therapy against lung cancer.

Boosting the photosensitization type I process will enhance the phototherapy efficacy because the superoxide radicals (O2-) generated during type I process are more toxic than the singlet oxygen (1O2) in type II process. Herein, [Ru(Hdtza)(phen)2][PF6] (1) and [Ru(pytz)(phen)2][PF6] (2) (phen = 1,10-phenanthroline) based on two nitrogen-rich tetrazole ligands, di(2H-tetrazol-5-yl) amine (H2dtza) and 5-(2-pyridyl)tetrazole (Hpytz) have been developed for photodynamic therapy (PDT) against lung cancer, respectively. Nanoprecipitation was used to prepare the nanoparticles (NPs) of both compounds. [Ru(Hdtza)(phen)2][PF6] NPs mainly undergo an electron transfer process to generate O2- while [Ru(pytz)(phen)2][PF6] the direct energy transfer to produce 1O2, which is responsible for the higher phototoxicity of [Ru(Hdtza)(phen)2][PF6] NPs (IC50 ~ 4.8 µg/mL) than that of [Ru(pytz)(phen)2][PF6] NPs (IC50 ~ 13.6 µg/mL) on human lung cancer cells (A549). Furthermore, in vivo study indicates that the tumor proliferation of nude mice can be effectively inhibited with the help of laser when the mice were injected with [Ru(pytz)(phen)2][PF6] NPs. This work may provide a simple strategy to design type I photosensitizers for enhanced photodynamic therapy.

Roles of aminoacyl-tRNA synthetase-interacting multi-functional proteins in physiology and cancer.

Aminoacyl-tRNA synthetases (ARSs) are an important class of enzymes with an evolutionarily conserved mechanism for protein synthesis. In higher eukaryotic systems, eight ARSs and three ARS-interacting multi-functional proteins (AIMPs) form a multi-tRNA synthetase complex (MSC), which seems to contribute to cellular homeostasis. Of these, AIMPs are generally considered as non-enzyme factors, playing a scaffolding role during MSC assembly. Although the functions of AIMPs are not fully understood, increasing evidence indicates that these scaffold proteins usually exert tumor-suppressive activities. In addition, endothelial monocyte-activating polypeptide II (EMAP II), as a cleavage product of AIMP1, and AIMP2-DX2, as a splice variant of AIMP2 lacking exon 2, also have a pivotal role in regulating tumorigenesis. In this review, we summarize the biological functions of AIMP1, EMAP II, AIMP2, AIMP2-DX2, and AIMP3. Also, we systematically introduce their emerging roles in cancer, aiming to provide new ideas for the treatment of cancer.

Current Study of RhoA and Associated Signaling Pathways in Gastric Cancer.

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5-year survival rate of early GC reaches 90%-95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.

TRIB3 promotes lung cancer progression by activating ß-catenin signaling.

TRIB3 roles in tumor progression have been revealed with similar or opposite results. Here, we found that TRIB3 expression was highly expressed in lung cancer tissues and correlated with tumor grades and metastasis. Functional experiments showed that TRIB3 knockdown (KD) inhibited lung cancer cell migration, invasion, EMT (epithelial-mesenchymal transition) process and stemness. Mechanistic studies demonstrated that TRIB3 physically interacted with ß-catenin and increased the recruitment of ß-catenin to the promoter region of genes regulated by Wnt. Re-activation of ß-catenin attenuated the inhibition of TRIB3 KD on lung cancer progression. These results suggest that TRIB3 interacts with ß-catenin and thus activates ß-catenin signaling, which is responsible for lung cancer progression, and blocking TRIB3 activity might be developed to treat lung cancer.

[Discussion on safety of Xanthii Fructus and consideration on its rational use].

Xanthii Fructus is a traditional Chinese medicine for the treatment of sinusitis and headache,rich in medicinal materials and is widely used for more than 1 800 years. Modern pharmacological studies have showed that Xanthii Fructus has anti-inflammatory,analgesic,anti-tumor,anti-bacterial,hypoglycemic,anti-allergic,immunomodulatory and other pharmacological effects,which can be commonly used in the treatment of diseases relating to immune abnormalities,such as rheumatoid arthritis,acute and chronic rhinitis,allergic rhinitis,and skin diseases,with a high medicinal value. Toxicological studies have shown that Xanthii Fructus poisoning can cause substantial damage to organs,such as the liver,kidney,and gastrointestinal tract,especially to liver. Because of the coexisting of its efficacy and toxicity,Xanthii Fructus often leads to a series of safety problems in the clinical application process. This study attempts to summarize its characteristics of adverse reactions,analyze the root cause of the toxicity of Xanthii Fructus from such aspects as processing,dose,course of treatment and eating by mistake,discuss the substance of its efficacy/toxicity from chemical compositions,and put forward exploratory thinking about how to promote its clinical rational application from the aspects such as strict processing,reasonable compatibility,medication information,contraindication,strict control of the dose,and course of treatment,so as to promote the safe and reasonable application of Xanthii Fructus.

Chi-miR-3031 regulates beta-casein via the PI3K/AKT-mTOR signaling pathway in goat mammary epithelial cells (GMECs).

BACKGROUND: MicroRNAs can regulate gene expression at the posttranscriptional level through translational repression or target degradation. Our previous investigations examined the differential expression levels of chi-miR-3031 in caprine mammary gland tissues in colostrum and common milk stages. RESULTS: The present study detected the role of chi-miR-3031 in the lactation mechanisms of GMECs. High-throughput sequencing was used to analyze transcriptomic landscapes of GMECs transfected with chi-miR-3031 mimics (MC) and a mimic negative control (NC). In the MC and NC groups, we acquired 39,793,503 and 36,531,517 uniquely mapped reads, respectively, accounting for 85.85 and 81.66% of total reads. In the MC group, 180 differentially expressed unigenes were downregulated, whereas 157 unigenes were upregulated. KEGG pathway analyses showed that the prolactin, TNF and ErbB signaling pathways, including TGFα, PIK3R3, IGF2, ELF5, IGFBP5 and LHß genes, played important roles in mammary development and milk secretion. Results from transcriptome sequencing, real-time PCR and western blotting showed that chi-miR-3031 suppressed the expression of IGFBP5 mRNA and protein. The expression levels of ß-casein significantly increased in the MC and siRNA-IGFBP5 groups. We observed that the down-regulation of IGFBP5 activated mTOR at the Ser2448 site in GMECs transfected with MC and siRNA-IGFBP5. Previous findings and our results showed that chi-miR-3031 activated the PI3K-AKT-mTOR pathway and increased ß-casein expression by down-regulating IGFBP5. CONCLUSIONS: These findings will afford valuable information for improving milk quality and contribute the development of potential methods for amending lactation performance.

Applications of gray-level variation detection method to intracellular ice formation.

Intracellular ice formation (IIF) is the major cause of death in cells subjected to freezing. The occurrence of intracellular ice prevents the penetration of light into the camera and makes the image dark. Therefore, the gray-level variation can reflect the IIF. However, cell deformation is accompanied with IIF, especially for larger cells. It is necessary to account this entire phenomenon together in a single method. In this paper, the normalized parameter C defined by the gray-level variation depending on the displacement was defined to reflect the gray-level change of each pixel point in the region of interest of the image. The process of IIF of onion epidermal cells and 293T cells was analyzed by this method.

Isoquercetin Ameliorates Cerebral Impairment in Focal Ischemia Through Anti-Oxidative, Anti-Inflammatory, and Anti-Apoptotic Effects in Primary Culture of Rat Hippocampal Neurons and Hippocampal CA1 Region of Rats.

Ischemic stroke is a major disability and cause of death worldwide due to its narrow therapeutic time window. Neuroprotective agent is a promising strategy to salvage acutely ischemic brain tissue and extend the therapeutic time window for stroke treatment. In this study, we aimed to evaluate the neuroprotective effects of isoquercetin in (1) primary culture of rat hippocampal neurons exposure on oxygen and glucose deprivation and reperfusion (OGD/R) injury and (2) rats subjected to transient middle cerebral artery occlusion and reperfusion (MCAO/R) injury. The results showed that isoquercetin post-treatment reduced the infarct size, number of apoptotic cells, oxidative stress, and inflammatory response after ischemia and reperfusion injury. The underlying mechanism study indicated that the neuroprotective effects of isoquercetin were elicited via suppressing the activation of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and caspase-1; the phosphorylation of ERK1/2, JNK1/2, and p38 mitogen-activated protein kinase (MAPK); and the secretion of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6. In addition, isoquercetin also effectively alleviated hippocampus neuron apoptosis by regulation of cyclic AMP responsive element-binding protein (CREB), Bax, Bcl-2, and caspase-3. Our report provided new considerations into the therapeutic action and the underlying mechanisms of isoquercetin to improve brain injury in individuals who have suffered from ischemic stroke. As a potent anti-inflammatory and anti-oxidative compound with neuroprotective capacities, the beneficial effects of isoquercetin when used to treat ischemic stroke and related diseases in humans warrant further studies.

Protection of seven dibenzocyclooctadiene lignans from Schisandra chinensis against serum and glucose deprivation injury in SH-SY5Y cells.

Dibenzocyclooctadiene lignans, the major active components of fruit of Schisandra chinensis (Turcz.) Baill., have been found to have activities that could prevent prostate and thyroid cancer, hepatotoxicity, oxidative stress-induced cerebral injury, etc. This study was conducted to evaluate the effects of seven dibenzocyclooctadiene lignans of Schisandra chinensis and explore the possible mechanisms in the human neuroblastoma SH-SY5Y cells exposed on serum and glucose deprivation (SGD) injury. The structure-activity relationships were also analyzed. Cell viability and lactate dehydrogenase (LDH) release were determined to evaluate cell injury. Inflammation and apoptosis-related protein levels were detected to elucidate the possible mechanisms. Schisantherin A, schizandrin C, and schizandrol B were found to have stronger protective effects than schizandrin A, schizandrin B, and schisanhenol in SH-SY5Y cells against SGD injury. Moreover, the protective effects of these lignans were possibly exhibited by regulating inflammation and apoptosis-related proteins in SH-SY5Y cells after SGD injury, supporting their beneficial effects for the prevention of cell injury in the pathogenesis of the central nervous system diseases, including ischemia stroke. The number and position of hydroxyl group and methylenedioxy in these lignans may be required for their effects.