Change of function and brain activity in patients of right spastic arm paralysis combined with aphasia after contralateral cervical seventh nerve transfer surgery.

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.

Effects of different fractions of polysaccharides from Dictyophora indusiata on high-fat diet-induced metabolic syndrome in mice.

Dictyophora indusiata is a common edible mushroom with great potential in the field of medicine against metabolic disorders, inflammation, and immunodeficiency. Our previous studies have shown that different fractions of the polysaccharide from Dictyophora indusiata (DIP) have various structural characteristics and morphology. However, the impact of the structural features on the protective effects of DIP against metabolic syndrome remains unclear. In this study, three distinct polysaccharide fractions have been extracted from Dictyophora indusiata and a high-fat diet-induced metabolic syndrome (MetS) was constructed in mice. The effects of these fractions on a range of MetS-associated endpoints, including abnormal blood glucose, lipid profiles, body fat content, liver function, intestinal microbiota and their metabolites were investigated. Through correlation analysis, the potential link between the monosaccharide composition of the polysaccharides and their biological activities was determined. The study aimed to explore the potential mechanisms and ameliorative effects of these polysaccharide fractions on MetS, thereby providing statistical evidence for understanding the relationship between monosaccharides composition of Dictyophora indusiata polysaccharides and their potential utility in treating metabolic disorders.

[Knockdown mitochondrial transcription factor A (TFAM) inhibits autophagy, proliferation, invasion and migration in human cervical cancer and osteosarcoma cells].

Objective To investigate the effects of mitochondrial transcription factor A (TFAM) on mitochondrial function, autophagy, proliferation, invasion, and migration in cervical cancer HeLa cells and osteosarcoma U2OS cells. Methods TFAM small-interfering RNA (si-TFAM) was transfected to HeLa and U2OS cells for downregulating TFAM expression. Mito-Tracker Red CMXRos staining combined with laser confocal microscopy was used to detect mitochondrial membrane potential (MMP). MitoSOXTM Red labeling was used to test mitochondrial reactive oxygen species (mtROS) levels. The expression of mitochondrial DNA (mtDNA) was detected by real-time quantitative PCR. Changes in the number of autophagosomes were detected by immunofluorescence cytochemistry. Western blot analysis was used to detect the expressions of TFAM, autophagy microtubule associated protein 1 light chain 3A/B (LC3A/B), autophagy associated protein 2A (ATG2A), ATG2B, ATG9A, zinc finger transcription factor Snail, matrix metalloproteinase 2 (MMP2) and MMP9. CCK-8 assay and plate clony formation assay were used to detect cell proliferation, while TranswellTM assay and scratch healing assay were used to detect changes in cell invasion and migration. Results The downregulation of TFAM expression resulted in a decrease in MMP and mtDNA copy number, but an increase in mtROS production. The protein content of LC3A/B decreased significantly compared to the control group and the number of autophagosomes in the cytoplasm decreased significantly. The expressions of ATG2B and ATG9A in the early stage of autophagy were significantly reduced. The expressions of Snail, MMP2 and MMP9 proteins in HeLa and U2OS cells were also decreased. The proliferation, invasion and migration ability of HeLa and U2OS cells were inhibited after being interfered with TFAM expression. Conclusion Downregulation of TFAM expression inhibits mitochondrial function, delays autophagy process and reduces the proliferation, invasion and migration ability of cervical cancer cells and osteosarcoma cells.

ML365 ameliorates postoperative cognitive impairment in aged mice by inhibiting NLRP3 inflammasome activation in the hippocampus.

The aim of this study was to examine the effects of ML365, a two-pore potassium channel (K2P) inhibitor, on postoperative cognitive impairment (POCD). A mouse model of POCD was constructed by subjecting aged C57BL/6 mice to exploratory laparotomy. Changes in cognitive function were assessed using the Morris water maze test. Western blotting and qPCR were used to detect hippocampal NLRP3, Caspase-1 and IL-1ß expression levels on days 3 and 7 post-surgery. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression level was also assessed by western blotting. Pathological changes and nerve damage in the hippocampal CA1 and CA3 regions were detected by H&E staining, while the concentration of malondialdehyde (MDA) in the plasma was measured. We found that pretreatment with ML365 (administered intraperitoneally at a dose of 10 mg/kg) 30 min prior to exploratory laparotomy effectively ameliorated POCD in mice. ML365 pretreatment also reduced NLRP3, Caspase-1, ASC and IL-1ß expression levels in the hippocampus, improved POCD-induced pathological changes in the hippocampal CA1 and CA3 areas of aged mice, and decreased levels of plasma MDA and oxidative stress. Together, our findings indicate that ML365 can alleviate POCD in mice by inhibiting NLRP3 inflammasome activation in the hippocampus.

Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a.

Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.

[miR-497 inhibits the growth and metastasis of SGC-7901 human gastric cancer anoikis resistant cells via blocking Wnt/ß-catenin signaling pathway].

Objective To investigate the effects of microRNA497 (miR-497) on the metastasis of gastric cancer and its possible molecular mechanism. Methods SGC-7901 gastric cancer parent cells were cultured in an ultra-low adhesion environment, and the anoikis resistance model of SGC-7901 cells was created after re-adhesion. Clone formation assay, flow cytometry, TranswellTM test and scratch healing test were used to detect the differences of biological behavior compared with their parent cells. Fluorescence quantitative PCR was performed to detect the expression of miR-497. Western blot analysis was used to detect the changes of key proteins of Wnt/ß-catenin signaling pathway and epithelial mesenchymal transformation (EMT) related proteins such as vimentin and E-cadherin. Parent cells and anoikis resistant SGC-7901 cells were transfected with miR-497 inhibitor or miR-497 mimic, and CCK-8 assay was used to detect the proliferation activity. TranswellTM invasion assay was performed to detect the invasion ability of cells. TranswellTM migration test and scratch healing assay was used to determine the migration ability. Western blot analysis was used to detect the expressions of Wnt1, ß-catenin, vimentin and E-cadherin. By transfecting miR-497 mimic into the anoikis resistance SGC-7901 cells and inoculating them subcutaneously in nude mice, the changes in the volume and mass of tumor tissues were measured and recorded. Western blot analysis was used to determine the expressions of Wnt1, ß-catenin, vimentin and E-cadherin of tumor tissues. Results Compared with the parent cells, the anoikis resistance SGC-7901 gastric cancer cells had faster proliferation rate, stronger colony formation, lower apoptosis rate, stronger invasion and migration ability. The expression of miR-497 was significantly decreased. After down-regulation of miR-497, the proliferation ability, invasion and migration ability were significantly enhanced. The expressions of Wnt1, ß-catenin and vimentin increased significantly, while E-cadherin decreased notably. The results of up-regulation miR-497 were the opposite. The tumor growth rate, tumor volume and mass of miR-497 overexpression group were significantly lower than those of control group. The expressions of Wnt1, ß-catenin and vimentin decreased significantly, while the expression of E-cadherin increased significantly. Conclusion The expression of miR-497 is low in the anoikis resistance SGC-7901 cells. miR-497 can inhibit the growth and metastasis of gastric cancer cells by blocking Wnt/ß-catenin signaling pathway and EMT.

TFAM knockdown undermines SQSTM1 mRNA stability but retards autophagy flux and inhibits tumor cells proliferation under starvation conditions.

Although starvation stress can alter the homeostasis of mitochondria and promote autophagy, there is still a lack of research focusing on the connection between them. In this study, we found that, accompanied by the upregulation of autophagy flux, the membrane mitochondrial potential (MMP), the content of reactive oxygen species (ROS), the production of ATP, and the copy number of mitochondrial DNA (mt-DNA) were changed when limiting amino acids supply. We screened and analyzed altered genes related to mitochondrial homeostasis under starvation stress and verified that the expression of mitochondrial transcription factor A (TFAM) was prominently upregulated. Inhibition of TFAM led to the change of mitochondrial function and homeostasis, caused the decrease of SQSTM1 mRNA stability and ATG101 protein level and restricted the autophagy process of cells under amino acid deficient conditions. In addition, the TFAM knockdown and starvation treatment aggravated the DNA damage and reduced proliferation rate of tumor cells. Therefore, our data shows the correlation between mitochondria homeostasis and autophagy, reveals the effect of TFAM on autophagy flux under starvation stress and provides experimental basis for the combined starvation therapy targeting mitochondria to inhibit tumor growth.

The effects of pectin on the gut microbiota and serum metabolites in mice fed with a high fat diet and exposed to low-dose antibiotics.

A sedentary lifestyle, unhealthy diet, and antibiotic use among other environmental factors have been associated with an increased incidence of metabolic disorders and inflammation, as well as gut dysbiosis. Pectin is an edible polysaccharide that exists widely in the cell wall of plants. Our previous study has shown that pectin with various degrees of esterification displayed different effects on preventing acute colitis and regulating the gut microbiome and serum metabolome. This study aimed to further explore the differential effects of pectin with various degrees of esterification on mice simultaneously treated with a high-fat diet and low-dose antibiotics. The results showed that low-esterified pectin L102 improved the biomarkers of metabolic disorders including blood glucose and body weight. The high-esterified pectin H121 and the low-esterified pectin L13 ameliorated inflammatory markers such as superoxide dismutase (SOD). The enrichment of probiotic bacteria such as Lactobacillus by pectin L102, reduction of conditional pathogens such as Klebsiella by pectin L13, and changes in circulating metabolites like L-tryptophan and 3-indoleacrylate by all three types of pectins were detected. These data provide evidence for a differential effect of different types of pectin on the gut microbiota and metabolic health.

Effects of three patterns of elevated CO2 in single and multiple generations on photosynthesis and stomatal features in rice.

BACKGROUND AND AIMS: Effects of elevated CO2 (E) within a generation on photosynthesis and stomatal features have been well documented in crops; however, long-term responses to gradually elevated CO2 (Eg) and abruptly elevated CO2 (Ea) over multiple generations remain scarce. METHODS: Japonica rice plants grown in open-top chambers were tested in the first generation (F1) under Ea and in the fifth generation (F5) under Eg and Ea, as follows: Ea in F1: ambient CO2 (A) + 200 µmol mol-1; Eg in F5: an increase of A + 40 µmol mol-1 year-1 until A + 200 µmol mol-1 from 2016 to 2020; Ea in F5: A + 200 µmol mol-1 from 2016 to 2020. For multigenerational tests, the harvested seeds were grown continuously in the following year in the respective CO2 environments. KEY RESULTS: The responses to Ea in F1 were consistent with the previous consensus, such as the occurrence of photosynthetic acclimation, stimulation of photosynthesis, and downregulation of photosynthetic physiological parameters and stomatal area. In contrast, multigenerational exposure to both Eg and Ea did not induce photosynthetic acclimation, but stimulated greater photosynthesis and had little effect on the photosynthetic physiology and stomatal traits. This suggests that E retained intergenerational effects on photosynthesis and stomatal features and that there were no multigenerational differences in the effects of Eg and Ea. CONCLUSIONS: The present study demonstrated that projecting future changes induced by E based on the physiological responses of contemporary plants could be misleading. Thus, responses of plants to large and rapid environmental changes within a generation cannot predict the long-term response of plants to natural environmental changes over multiple generations, especially in annual herbs with short life cycles.

Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota.

Hyperlipidemia can directly cause metabolic diseases that seriously endanger disorder and metabolism and gut health. Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). The above results provided new insights into the hypolipidemic mechanism of TP and EGCG.

The determiner of photosynthetic acclimation induced by biochemical limitation under elevated CO2 in japonica rice.

Photosynthetic acclimation to prolonged elevated CO2 could be attributed to the two limited biochemical capacity, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) carboxylation and ribulose-1,5-bisphosphate (RuBP) regeneration, however, which one is the primary driver is unclear. To quantify photosynthetic acclimation induced by biochemical limitation, we investigated photosynthetic characteristics and leaf nitrogen allocation to photosynthetic apparatus (Rubisco, bioenergetics, and light-harvesting complex) in a japonica rice grown in open-top chambers at ambient CO2 and ambient CO2+200 µmol mol-1 (e [CO2]). Results showed that photosynthesis was stimulated under e [CO2], but concomitantly, photosynthetic acclimation obviously occurred across the whole growth stages. The content of leaf nitrogen allocation to Rubisco and biogenetics was reduced by e [CO2], while not in light-harvesting complex. Unlike the content, there was little effects of CO2 enrichment on the percentage of nitrogen allocation to photosynthetic components. Additionally, leaf nitrogen did not reallocate within photosynthetic apparatus until the imbalance of sink-source under e [CO2]. The contribution of biochemical limitations, including Rubisco carboxylation and RuBP regeneration, to photosynthetic acclimation averaged 36.2% and 63.8% over the growing seasons, respectively. This study suggests that acclimation of photosynthesis is mainly driven by RuBP regeneration limitation and highlights the importance of RuBP regeneration relative to Rubisco carboxylation in the future CO2 enrichment.

Hepatic metabolism-related effects of polysaccharides from red kidney bean and small black soybean on type 2 diabetes.

In our previous study, two crude polysaccharides from red kidney bean and small black soybean (RK, SB) have shown the alleviative effect on type 2 diabetic mice. Meanwhile, hepatic dysfunction usually accompanied with type 2 diabetes mellitus (T2DM), and closely related to glucose and lipid homeostasis. Therefore, this time we further investigated the protective effect on hepatic dysfunction of RK and SB. Results found that both crude polysaccharides had the protective effects. In addition, investigation on purified polysaccharides identified that the polysaccharide was the biofunctional component basis in crude RK and SB. Subsequently, further research investigated the regulating mechanism of two pure polysaccharides (RKPH and SBPH) on hepatic metabolism and lipid metabolism. The results showed the improved different metabolites of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by RKPH and SBPH to affect glycerophospholipid metabolism pathway might be involved in the improvement of the glucose, lipids homeostasis and liver function in T2DM.

LINC02875 Upregulation Contributed to Poor Prognosis for the Hepatocellular Carcinoma and Progression for the Cancerous Cells.

The prognostic implications and physiological effect of LINC02875 are unknown in hepatocellular carcinoma (HCC). We sought to examine the prognostic value of LINC02875 in HCC and assessed its role in HCC cellular function. LINC02875 expression was evaluated by RT-qPCR in HCC specimens and cell lines. LINC02875 expression was subjected to assess the correlation with clinical parameters by Chi-squared test and overall survival by Kaplan - Meier curve and Cox regression analysis. The effects of LINC02875 on the biological characteristics of HCC cells were studied by MTS and Transwell assay. LINC02875 was high-expressed in HCC, and this was associated with unfavorable clinical features and poor prognosis of HCC, especially HBV-related HCC. Knockdown of LINC02875 inhibited the proliferation, migration, and invasion of HCC cells. miR-485-5p was a downstream microRNA of LINC02875. LINC02875 affects the prognosis of HCC patients, especially HBV-related ones. LINC02875 represents a suitable therapeutic target for HCC.

Impact of lncRNA SOX9-AS1 overexpression on the prognosis and progression of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a latent and malignant tumor with a dismal prognosis. This study was to evaluate the clinical relevance and therapeutic potential of SOX9-AS1 expression in ICC. METHODS: The cancerous tissues and adjacent normal tissues were collected from ICC patients. Blood samples from ICC, hepatocellular carcinoma (HCC) group, the extrahepatic cholangiocarcinoma (ECC) group and the healthy controls were collected. SOX9-AS1 levels were evaluated in tissues (versus normal tissues) and plasma samples (versus plasma from HCC and ECC by quantitative real-time RT-PCR. The diagnostic value of SOX9-AS1 for ICC was estimated using receiver operating characteristic (ROC) curves. The relevancy between SOX9-AS1 expression and overall survival or recurrence-free survival was assessed by Kaplan-Meier curves multivariate analyses. The overexpression and knockdown of SOX9-AS1 on cell behavior were assessed by CCK-8 and transwell assay. RESULTS: SOX9-AS1 levels were increased in ICC, both in the tissues and the cell lines. The upregulation of SOX9-AS1 showed a highly discriminative profile, distinguishing ICC patients from healthy subjects or HCC or ECC patients. Upregulation of SOX9-AS1 was related to shorter overall survival and recurrence-free survival. Muli-variate analysis revealed that SOX9-AS1 expression was an independent prognostic purpose factor of worst overall survival and recurrence-free survival. CONCLUSIONS: SOX9-AS1 drives tumor growth and metastasis in ICC. SOX9-AS1 may be applied as a new diagnostic and prognostic purposed marker, in addition to a promising therapeutic target in ICC.

miR-517b-3p promotes the progression of portal vein tumor thrombus via activating Wnt/ß-catenin signaling pathway in hepatocellular carcinoma.

AIMS: This study was aimed to investigate the expression patterns and prognostic value of microRNA-517b-3p (miR-517b-3p) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). METHODS: The expression of miR-517b-3p in PVTT tissues and cells was estimated using qRT-PCR. Through Kaplan-Meier survival analysis, Cox regression assay and ROC analysis, the significance of miR-517b-3p was explored. In addition, cell experiments were performed to examine the functional role of miR-517b-3p during progression of PVTT. Moreover, the biological process and biological pathway analysis analyses were conducted through GSEA and FunRich. Besides, the protein-protein interaction (PPI) network of the DEGs was established through cBioPortal website. RESULTS: Compared with the controls, the miR-517b-3p was upregulated in both PVTT tissues and cells. The upregulated miR-517b-3p, which served as a potential diagnostic biomarker to distinguish PVTT from PT and controls, was associated with poor overall survival and acted as an independent prognostic factor. The cell proliferation, migration and invasion were proved to be enhanced by overexpression of miR-517b-3p. Furthermore, Wnt/ß-catenin signaling was suppressed by miR-517b-3p knockdown and might be involved in the progression of PVTT. CONCLUSION: miR-517b-3p may promote PVTT cell proliferation, migration and invasion via activation of Wnt/ß-catenin signaling pathway. Meanwhile, miR-517b-3p has overexpression in PVTT samples, and serves as a candidate diagnostic and prognostic biomarker in HCC patients with PVTT.

Impact of pectin with various esterification degrees on the profiles of gut microbiota and serum metabolites.

Colitis is generally affected by multiple factors, including the dysbiosis of intestinal microbiota, and may affect organs outside colon through circulation. Pectin, which is an edible polysaccharide widely present in plant cell walls, has been proved in our previous study to possess preventive potentials against acute ulcerative colitis, especially when the esterification degree is less than 50%. This study aimed to clarify the underlying correlations of gut microbiome and serum metabolites with the preventive effects of pectin with different esterification degrees (H121, L13, and L102) against colitis in mice. MiSeq sequencing data showed that symbiotic bacteria especially beneficial Lactobacillus and Bifidobacterium were enriched by pectin intake. Fiber consumers such as Prevotella and Bacteroides actively responded to L13 pectin, particularly under high dosage (L13-H). In addition, the abnormal abundance of Akkermansia associated with colitis would not appear in mice who had been provided with any of the three pectins before dextran sulfate sodium (DSS) treatment. Furthermore, pre-treatment of H121 and L13 pectins could improve the serum glycerophospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE). In contrast, lysophosphatidic acid (LPA) contributing to the glycerophospholipid metabolism pathway was enriched only in the L13-H group, which has been previously proved to be associated with the epithelial barrier and intestinal homeostasis. Positive relationships between the glycerophospholipids and the dominant candidates of intestinal bacteria such as Lactobacillus indicated the joint actions of intestinal microbes and serum metabolites as well as the underlying crosstalks among gut microbiome. Therefore, the results of this research suggested that the preventive effects of low-esterified pectin on DSS-induced colitis were likely to be initiated by the enrichment of probiotics in the gut and serum glycerophospholipids. KEY POINTS: • L13 pectin remarkably improved the diversity of the gut microbiome in healthy mice. • Probiotics were enriched and abnormal Akkermansia was restored by L13 and L102 pectins. • Glycerophospholipid metabolism was significantly enriched by H121 and L13 pectins.

The Hua-Shan rehabilitation program after contralateral seventh cervical nerve transfer for spastic arm paralysis.

PURPOSE: To propose the novel Hua-Shan rehabilitation program for patients undergoing the contralateral seventh cervical nerve transfer, and explore the influence of different rehabilitation on the postoperative recovery. MATERIALS AND METHODS: The Hua-Shan program was established in consideration of the three elements: the nerve regeneration, brain plasticity and group therapy. Its effect was evaluated by comparing the postoperative recovery of the hemorrhagic stroke survivors among the following three groups: Group A-standard Hua-Shan program after surgery; Group B-standard traditional program after surgery; Group C-no standard rehabilitation after surgery. RESULTS: Significantly better functions after surgery were detected in all the groups, while the absence of standard rehabilitation massively offset the benefits of the surgery. Furthermore, the Hua-Shan program showed advantage over the traditional rehabilitation, which may largely be attributed to its improvements for the fine action of wrist&finger. CONCLUSIONS: The Hua-Shan program provided the opportunity to maximize the benefits of contralateral seventh cervical nerve transfer.IMPLICATIONS FOR REHABILITATIONStandard rehabilitation plays key roles in the recovery process for patients undergoing contralateral seventh cervical nerve transfer.The Hua-Shan program targeting nerve regeneration, brain plasticity and group therapy further improved the benefits of patients undergoing contralateral seventh cervical nerve transfer.

LncRNA SNHG7 Regulates Mesenchymal Stem Cell Through the Notch1/Jagged1/Hes-1 Signaling Pathway and Influences Folfirinox Resistance in Pancreatic Cancer.

Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. In vitro and in vivo sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC co-culture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance via the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients.

Targeting the membrane fusion event of human respiratory syncytial virus with rationally designed α-helical hairpin traps.

AIMS: Rational design of protein scaffolds with specific biological functions/activities has attracted much attention over the past decades. In the present study, we systematically examine the trimer-of-hairpins (TOH) motif of human respiratory syncytial virus (RSV) F protein, which plays a central role in viral membrane fusion and is a coiled-coil six-helix bundle formed by the antiparallel intermolecular interaction between three N-terminal heptad-repeat (HRN) helices and three C-terminal heptad-repeat (HRC) helices. MAIN METHODS: A rational strategy that integrates dynamics simulation, thermodynamics calculation, fluorescence polarization and circular dichroism is proposed to design HRC-targeted α-helical hairpin traps based on the crystal template of HRN core. KEY FINDINGS: The designed hairpin traps possess a typical helix-turn-helix scaffold that can be stabilized by stapling a disulfide bridge across its helical arms, which are highly structured (helicity >60%) and can mimic the native spatial arrangement of HRN helices in TOH motif to trap the hotspot sites of HRC with effective affinity (Kd is up to 6.4 µM). SIGNIFICANCE: The designed α-helical hairpin traps can be used as lead entities for further developing TOH-disrupting agents to target RSV membrane fusion event and the proposed rational design strategy can be readily modified to apply for other type I viruses.