Spinal cord injury: Olfactory ensheathing cell-based therapeutic strategies.

Spinal cord injury (SCI) is a highly disabling neurological disorder that is difficult to treat due to its complex pathophysiology and nerve regeneration difficulties. Hence, effective SCI treatments are necessary. Olfactory ensheathing cells (OECs), glial cells derived from the olfactory bulb or mucosa, are ideal candidates for SCI treatment because of their neuroprotective and regenerative properties, ample supply, and convenience. In vitro, animal model, and human trial studies have reported discoveries on OEC transplantation; however, shortcomings have also been demonstrated. Recent studies have optimized various OEC transplantation strategies, including drug integration, biomaterials, and gene editing. This review aims to introduce OECs mechanisms in repairing SCI, summarize the research progress of OEC transplantation-optimized strategies, and provide novel research ideas for SCI treatment.

Increased resected lymph node stations improved survival of esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT. METHODS: The hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used. RESULTS: In total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84-0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84-0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups. CONCLUSION: This cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.

Second harmonic generation by matching the phase distributions of topological corner and edge states.

Second harmonic generation (SHG) in topological photonic crystals is chiefly concerned with frequency conversion between the same topological states. However, little attention has been paid to the effect of coupling between different topological states on the SHG. In this study, we propose a method for achieving optimal SHG in a topological cavity by matching the phase distributions of the electric fields of the topological corner state (TCS) and topological edge state (TES). Our results show that the intrinsic efficiency can be improved when the phase distributions of the fundamental wave within the TCS and the second harmonic wave within the TES have the same symmetry. Otherwise, conversion efficiency will be greatly inhibited. With this method, we achieved an optimal intrinsic efficiency of 0.165%. Such a platform may enable the development of integrated nanoscale light sources and on-chip frequency converters.

Multi-topological state via the Brillouin zone overlap for nonlinear frequency conversion.

Multiband topological edge states (TESs) or topological corner states (TCSs) in photonic crystals provide effective ways to manipulate the nonlinear frequency conversions. However, the deliberate design and the limited number of multibands lead to the difficulty of experimental realization of the topological nonlinear frequency conversion or higher harmonic generation. Here, we propose an effective method to achieve multiple TESs and TCSs by combining the Brillouin zones of multiple different systems. It is shown that the spectra of the subsystems disperse into different energy levels due to the inter-system hopping. Based on this approach, we construct a topological photonic crystal based on the Brillouin zone overlapped SSH model, which enables the overlapped TCSs to participate in nonlinear frequency conversion. Our scheme can provide a significant way to realize the topological nonlinear frequency conversion with double resonances or multiple resonances.

The prognostic role of coagulation markers in the progression and metastasis of laryngeal squamous cell carcinoma.

BACKGROUND: The application of coagulation-related markers in laryngeal squamous cell carcinoma(LSCC) remains unclear. This study explored the prognostic role of coagulation markers in the progression and metastasis of LSCC. METHODS: Coagulation markers of patients with LSCC receiving surgery in the Second Affiliated Hospital of Fujian Medical University in China, from January 2013 to May 2022 were retrospectively analyzed and compared with those of contemporary patients with benign laryngeal diseases. The relationship between clinicopathological features of LSCC and coagulation markers was analyzed with the chi-square and rank sum tests. The ROC curve analysis was utilized to evaluate the diagnostic efficacy of seven coagulation markers for LSCC and its different clinicopathological features, and to find the optimal cutoff value of each coagulation marker. RESULTS: 303 patients with LSCC and 533 patients with benign laryngeal diseases were included in the present analysis. Compared to the control group, prothrombin time (PT) (p < 0.001), activated partial thromboplastin time (APTT) (p = 0.001), and Fib (p < 0.001) in patients with LSCC were significantly higher, while mean platelet volume (MPV) (p < 0.001) was significantly shorter. Significant increases were detected in PT (Z = 14.342, p = 0.002), Fib (Z = 25.985, p < 0.001), platelet count (PC) (Z = 12.768, p = 0.005), PCT (Z = 9.178, p = 0.027), MPV (F = 2.948, p = 0.033) in T4 stage. Fib had the highest prognostic value among the seven coagulation markers in different T stages (AUC = 0.676, p < 0.001), N stages (AUC = 0.717, p < 0.001), tumor stage (AUC = 0.665, p < 0.001), differentiation degree (AUC = 0.579, p = 0.022), and neurovascular invasion (AUC = 0.651, p = 0.007). Fib (Z = 25.832, p < 0.001), PC (Z = 23.842, p < 0.001), and PCT (Z = 20.15, p < 0.001) in N1 and N3 stages were significantly higher than in N0 stage. PT (Z = 12.174, p = 0.007), Fib (Z = 23.873, p < 0.001), PC (Z = 17.785, p < 0.001), and PCT (Z = 14.693, p = 0.002) were significantly higher in stage IV than in stage I and II. APTT (Z=-1.983, p = 0.047), Fib (Z=-2.68, p = 0.007), PC (Z=-2.723, p = 0.006), and PCT (Z=-2.592, p = 0.01) increased significantly when the tumor invaded neurovascular tissue. CONCLUSIONS: Coagulation markers have the potential to act as biomarkers for predicting pathological features of LSCC. The high level of Fib was helpful for the diagnosis of LSCC and the detection of advanced LSCC. TRIAL REGISTRATION: Not applicable.

Learning curve for inflatable mediastinoscopic and laparoscopic-assisted esophagectomy.

OBJECTIVE: To identify the morbidity that is associated with the learning curve of inflatable mediastinoscopic and laparoscopic-assisted esophagectomy (IMLE), and investigate the strategies to ride out the early period. METHODS: Our study included a retrospective series of 108 consecutive patients undergoing IMLE by a single surgeon with advanced training in minimally invasive esophageal surgery in independent practice at high-volume tertiary center from July 2017 to November 2020. The cumulative sum (CUSUM) method was used to analyze the learning curve. Patients were stratified into two groups in chronological order, defining the surgeon's early (Group 1: the first 27 cases) and late experience (Group 2: the next 81 cases). Intraoperative characteristics and short-term surgical outcomes were compared between the two groups. RESULTS: A total of 108 patients were included. Three patients converted into thoracoscopic surgery. The number of patients with postoperative pulmonary infection was 16 (14.8%), and vocal cord palsy had occurred in 12 patients (11.1%). One patient died within 90 days after surgery. CUSUM plots revealed decreasing total operative time, thoracic procedure time, abdominal procedure time, assistant-adjustment time after patients 27, 17, 26, and 35, respectively. CONCLUSION: IMLE is technically feasible, in terms of perioperative outcomes, for using as a radical surgery for thoracic esophageal cancer. For a surgeon experienced in minimally invasive esophageal surgery, experience of 27 cases is required to gain early proficiency of IMLE.

Left-primary & right-auxiliary operation mode in mediastinoscope-assisted radical esophagectomy.

BACKGROUND: Mediastinoscope-assisted transhiatal esophagectomy (MATHE) is the most minimally invasive esophagectomy procedure. It is a more challenging procedure and more difficult to be popularized than thoracoscopic surgery. We developed a new MATHE operation mode that provides a clearer visual field and makes the procedures simpler. METHODS: A total of 80 patients with esophageal cancer were divided into a control group (n = 29) and a study group (n = 51). The control group underwent classic MATHE, while the study group received modified MATHE. We compared the two groups on operation time; intraoperative blood loss; blood transfusion amount; incidence rate of lung infection, recurrent laryngeal nerves (RLNs) injury, chylothorax, and anastomotic leakage; and upper mediastinal lymph node dissection. RESULTS: The study group was significantly better than the control group in operation time (271.78 min vs. 322.90 min, p < 0.05), intraoperative blood loss (48.63 mL vs. 68.97 mL, p < 0.05), and left paratracheal lymph node (No. 4L) dissection rate (88.24% vs. 24.14%, p < 0.01). No significant differences were identified in the incidence rate of anastomotic leakage, lung complications, or RLNs injury between the two groups. CONCLUSION: The modified MATHE is easier to perform. Modified MATHE is significantly superior to classic MATHE in operation time, intraoperative blood loss, and upper mediastinal lymph node dissection rate.

Migration-inducing gene-7 promotes glioma cell proliferation and invasiveness via activating the MAPK signaling pathway.

Glioma is a highly aggressive primary malignant tumor. Migration-inducing gene-7 (Mig-7) is closely related to tumor invasion and metastasis. However, the detailed molecular mechanism of Mig-7-mediated promotion of glioma cell invasion requires further investigation. Therefore, this study aimed to investigate the molecular mechanism by which Mig-7 promotes invasion and growth of glioma tumor cells. After collecting 65 glioma tissues and 16 non-tumor tissues, the expression difference of Mig-7 between tumor tissues and non-tumor tissues was analyzed. The molecular mechanism of Mig-7 in tumor cells was investigated by knockdown or overexpression of Mig-7 in U87MG cells. Specifically, the expression levels of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules were detected in cells that knocked down Mig-7. MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). The effect of Mig-7 on the tumorigenic ability of U87MG cells was investigated by subcutaneous tumorigenic experiment in nude mice. The corresponding results indicated that Mig-7 expression was significantly higher in glioma tissues and cell lines compared to that in non-neoplastic brain tissues and normal glial cell lines. In U87MG cells, downregulation or overexpression of Mig-7 inhibited or promoted the expression of MMP-2, MMP-9, LAMC2, EphA2, and VE-cadherin, and phosphorylation levels of ERK1/2, JNK, and p38. Mig-7 overexpression promoted migration, invasion, cell viability, and tube formation, which were reversed by the MAPK signaling pathway inhibitors. Mig-7 overexpression promoted subcutaneous tumor growth in mice and upregulated the phosphorylation levels of ERK1/2, JNK, and p38 and the expression of Ki-67. These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.

Transradial versus transfemoral access for endovascular therapy of intracranial aneurysms: a systematic review and meta-analysis of cohort studies.

Endovascular treatment is widely used in the treatment of intracranial aneurysms. However, neurosurgeons are sceptical about endovascular access via the radial artery. We performed a systematic review and meta-analysis to compare the effectiveness and safety of transradial and transfemoral artery access in patients with intracranial aneurysms. We systematically searched the PubMed, Embase, and Cochrane databases for studies comparing the two approaches. The primary outcome was total complications, and the secondary outcomes were access site complications, intracranial haemorrhage, stroke, thromboembolism, silent infarct, re-treatment rate, mortality, complete occlusion of intracranial aneurysms, procedure duration, and length of hospital stay. A random-effects model was used to assess the pooled data. Of the 100 identified studies, 6 were eligible (a total of 3764 participants). There were no significant differences in total complications(odds ratio [OR] = 0.69, 95% confidence interval [CI] [0.33, 1.45], p = 0.32), complete occlusion of intracranial aneurysms (OR = 1.02, 95%CI [0.77,1.37], p = 0.87), procedure duration (mean difference [MD] = - 6.24, 95%CI [- 14.75, - 1.54], p = 0.95), or length of hospital stay (MD = 2.204, 95%CI [- 0.05, 4.45], p = 0.95), access site complications (OR = 0.49, 95%CI [0.16, 1.52], p = 0.22), intracranial haemorrhage (OR = 1.07, 95%CI [0.49, 2.34], p = 0.86), stroke (OR = 0.59, 95%CI [0.20, 1.77], p = 0.35), thromboembolism (OR = 0.85, 95%CI [0.33, 2.17], p = 0.74), silent infarct (OR = 0.69, 95%CI [0.04, 11.80], p = 0.80), retreatment rate (OR = 1.32, 95%CI [0.70, 2.48], p = 0.39), mortality (OR = 1.41, 95%CI [0.06, 5.20], p = 0.61), immediate occlusion (OR = 0.99, 95%CI [0.64, 1.51], p = 0.95), and occlusion during follow-up (OR = 1.10, 95%CI [0.56, 2.16], p = 0.74) between the transradial and transfemoral groups. This study showed comparable safety and efficacy outcomes between transradial and transfemoral access in patients with intracranial aneurysms treated endovascularly. Future large randomised trials are warranted to confirm these findings.

Enantiomerically Enriched α-Borylzinc Reagents by Nickel-Catalyzed Carbozincation of Vinylboronic Esters.

In this paper is described a synthesis of enantiomerically enriched, configurationally stable organozinc reagents by catalytic enantioselective carbozincation of a vinylboronic ester. This process furnishes enantiomerically enriched α-borylzinc intermediates that are shown to undergo stereospecific reactions, producing enantioenriched secondary boronic ester products. The properties of the intermediate α-borylzinc reagent are probed and the synthetic utility of the products is demonstrated by application to the synthesis of (-)-aphanorphine and (-)-enterolactone.

Dynamically reconfigurable topological states in photonic crystals with liquid crystals.

Dynamically tunable and reconfigurable topological states are realized in higher-order topological insulators with the liquid crystal (LC). By changing the loading voltage of the LC, the eigenfrequency of the edge and corner states can be tuned, but even more important is that the edge state and corner state with the same frequency are realized. Based on this reconfigurability of topological states, optical routers and lasers with multiple topological states can be realized. Our results may be applied to topological optical circuits and provide new ideas for optical field localization and manipulation.

Long non-coding RNA PSMA3-AS1 promotes glioma progression through modulating the miR-411-3p/HOXA10 pathway.

BACKGROUND: Glioma is a common type of brain tumor and is classified as low and high grades according to morphology and molecules. Growing evidence has proved that long non-coding RNAs (lncRNAs) play pivotal roles in numerous tumors or diseases including glioma. Proteasome 20S subunit alpha 3 antisense RNA 1 (PSMA3-AS1), as a member of lncRNAs, has been disclosed to play a tumor-promoting role in cancer progression. However, the role of PSMA3-AS1 in glioma remains unknown. Therefore, we concentrated on researching the regulatory mechanism of PSMA3-AS1 in glioma. METHODS: PSMA3-AS1 expression was detected using RT-qPCR. Functional assays were performed to measure the effects of PSMA3-AS1 on glioma progression. After that, ENCORI ( http://starbase.sysu.edu.cn/ ) database was used to predict potential genes that could bind to PSMA3-AS1, and miR-411-3p was chosen for further studies. The interaction among PSMA3-AS1, miR-411-3p and homeobox A10 (HOXA10) were confirmed through mechanism assays. RESULTS: PSMA3-AS1 was verified to be up-regulated in glioma cells and promote glioma progression. Furthermore, PSMA3-AS1 could act as a competitive endogenous RNA (ceRNA) for miR-411-3p to regulate HOXA10 and thus affecting glioma progression. CONCLUSION: PSMA3-AS1 stimulated glioma progression via the miR-411-3p/HOXA10 pathway, which might offer a novel insight for the therapy and treatment of glioma.

SOAPTyping: an open-source and cross-platform tool for sequence-based typing for HLA class I and II alleles.

BACKGROUND: The human leukocyte antigen (HLA) gene family plays a key role in the immune response and thus is crucial in many biomedical and clinical settings. Utilizing Sanger sequencing, the golden standard technology for HLA typing enables accurate identification of HLA alleles in high-resolution. However, only the commercial software, such as uTYPE, SBT-Assign, and SBTEngine, and very few open-source tools could be applied to perform HLA typing based on Sanger sequencing. RESULTS: We developed a user-friendly, cross-platform and open-source desktop application, known as SOAPTyping, for Sanger-based typing in HLA class I and II alleles. SOAPTyping can produce accurate results with a comprehensible protocol and featured functions. Moreover, SOAPTyping supports a more advanced group-specific sequencing primers (GSSP) module to solve the ambiguous typing results. We used SOAPTyping to analyze 36 samples with known HLA typing from the University of California Los Angeles (UCLA) International HLA DNA Exchange platform and 100 anonymous clinical samples, and the HLA typing results from SOAPTyping are identical to the golden results and 5.5 times faster than commercial software uTYPE, which shows the usability of SOAPTyping. CONCLUSIONS: We introduce the SOAPTyping as the first open-source and cross-platform HLA typing software with the capability of producing high-resolution HLA typing predictions from Sanger sequence data.

The Role and Prognostic Significance of Aortopulmonary, Anterior Mediastinal, and Tracheobronchial Lymph Nodes in Esophageal Cancer: Update of the Eighth-Edition TNM Staging System (2018).

BACKGROUND: The eighth edition of TNM staging for esophageal cancer will be implemented at 2018. The stations 5, 6, and 10 lymph nodes (LNs) have been omitted from the regional lymph node map for the new TNM staging. However, the role and prognostic significance of these LN stations were not clear. The purpose of this study was to investigate whether the revised nodal staging is appropriate and to verify the role, prognostic significance, and therapeutic value of these LNs in esophageal cancer. METHODS: The records of patients who underwent esophagectomy for cancer in our department between 2007 and 2013 were retrospectively analyzed. The rate of metastases was calculated for stations 5, 6, and 10 LNs. LN metastasis and patient survival were analyzed. RESULTS: A total of 1637 patients were included. The calculated rate of metastasis to stations 5, 6, and 10 was 3.2%, 2.3%, and 4.9%, respectively. No difference was found in the N stage determined by the seventh and eighth edition N staging systems. The status of station 5, 6, or 10 was not associated with long-term survival according to Cox proportional hazards model analysis. CONCLUSIONS: Metastasis to stations 5, 6, or 10 LNs was infrequent. Omitting of stations 5, 6, and 10 LNs in the eighth edition TNM staging did not influence the accuracy and survival-predicting efficacy. The therapeutic value of lymphadenectomy of stations 5, 6, and 10 was limited. The status of stations 5, 6, and 10 LNs was not associated with long-term survival.

End-to-End Versus End-to-Side Hand-Sewn Anastomosis for Minimally Invasive McKeown Esophagectomy.

BACKGROUND: Standard anastomotic configuration for esophagogastric anastomosis is not conclusive. This study aimed to compare the short-term outcomes of end-to-end (ETE) cervical double-layer hand-sewn anastomoses with those of end-to-side (ETS) anastomoses for minimally invasive McKeown esophagectomy. METHODS: Between January 2016 and December 2017, the clinical data of 252 consecutive patients who underwent minimally invasive esophagectomy were reviewed retrospectively. The 252 patients comprised 130 patients in the ETS group and 122 patients in the ETE group. The same surgical procedures were applied in both groups, except for esophagogastric reconstruction. Short-term outcomes including leakage, stricture, reflux, operative features, and other surgical complications were analyzed for a comparison of the two configurations. RESULTS: The ETS and ETE groups did not differ significantly in terms of leakage rate (P = 0.34), anastomotic stricture rate (P = 0.70), or postoperative reflux (P = 0.66). However, the ETS group had a longer operation time (P = 0.011), a longer anastomosis time (P < 0.001), and a longer postoperative hospital stay (P = 0.009) than the ETE group, and the postoperative gastric dilation rates were lower in ETE group than in the ETS group (P = 0.025). The two groups did not differ significantly in terms of other postoperative complications. CONCLUSIONS: The major postoperative complications were comparable for the two anastomotic configurations. However, the patients with ETE anastomosis showed a favorable outcome in terms of a decreasing postoperative thoracic gastric dilation rate. End-to-end anastomosis also seemed to have slight advantages in terms of shorter operation and anastomosis times as well as a shorter postoperative hospital stay.

Single-Port Thoracoscopic Minimally Invasive Esophagectomy for Esophageal Cancer.

BACKGROUND: This study was to explore the safety and feasibility of single-port thoracoscopic esophagectomy for esophageal cancer. METHODS: The patients were placed in left lateral prone position, and a 4-cm incision through the 4th-5th intercostal space was taken on the post-axillary line. Except for a surgical wound protector, no other special instruments were used for single-port technique. The 10-mm camera and two or three thoracoscopic instruments were used for the thoracic phase. Mobilization of stomach with celiac lymph node dissection was performed via multiple-port laparoscopic approach. Cervical double-layered anastomosis was completed by hand-sewn technique. RESULTS: A total of twenty-eight patients with esophageal squamous cell carcinoma underwent the single-port thoracoscopic surgery. All of the patients underwent R0 resection. The median time taken for thoracic phase and total operation time were 126 min (range, 121-153) and the 253 min (range, 197-309), respectively. The median number of resected thoracic lymph nodes was 16 (range, 12-24). There were no deaths or severe postoperative complications in this study, with no conversion of minimally invasive surgery to open procedure. CONCLUSIONS: Our preliminary results demonstrate that this technique is safe and feasible for treating esophageal cancer within an acceptable length of operation time, which does not compromise the surgical radicality.

Identification of Denatured Biological Tissues Based on Time-Frequency Entropy and Refined Composite Multi-Scale Weighted Permutation Entropy during HIFU Treatment.

Identification of denatured biological tissue is crucial to high intensity focused ultrasound (HIFU) treatment. It is not easy for intercepting ultrasonic scattered echo signals from HIFU treatment region. Therefore, this paper employed time-frequency entropy based on generalized S-transform (GST) to intercept ultrasonic echo signals. First, the time-frequency spectra of ultrasonic echo signal is obtained by GST, which is concentrated around the real instantaneous frequency of the signal. Then the time-frequency entropy is calculated based on time-frequency spectra. The experimental results indicate that the time-frequency entropy of ultrasonic echo signal will be abnormally high when ultrasonic signal travels across the boundary between normal region and treatment region in tissues. Ultrasonic scattered echo signals from treatment region can be intercepted by time-frequency entropy. In addition, the refined composite multi-scale weighted permutation entropy (RCMWPE) is proposed to evaluate the complexity of nonlinear time series. Comparing with multi-scale permutation entropy (MPE) and multi-scale weighted permutation entropy (MWPE), RCMWPE not only measures complexity of signal including amplitude information, but also improves the stability and reliability of multi-scale entropy. The RCMWPE and MPE are applied to 300 cases of actual ultrasonic scattered echo signals (including 150 cases in normal status and 150 cases in denatured status). It is found that the RCMWPE and MPE values of denatured tissues are higher than those of the normal tissues. Both RCMWPE and MPE can be used to distinguish normal tissues and denatured tissues. However, there are fewer feature points in the overlap region between RCMWPE of denatured tissues and normal tissues compared with MPE. The intra-class distance and the inter-class distance of RCMWPE are less and greater respectively than MPE. The difference between denatured tissues and normal tissues is more obvious when RCMWPE is used as the characteristic parameter. The results of this study will be helpful to guide doctors to obtain more accurate assessment of treatment effect during HIFU treatment.

The role of mitochondrial folate enzyme MTHFD1L in esophageal squamous cell carcinoma.

OBJECTIVE: The lack of novel therapeutic targets poses the major challenge to prolong survival and improve the quality of life for esophageal squamous cell carcinoma (ESCC). Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) plays critical roles in folate cycle maintenance. However, little information is available concerning the role of MTHFD1L in cancer cells, and no studies have addressed such issues in esophageal cancer. MATERIALS AND METHOD: Surgical cancer and adjacent normal esophageal tissues were obtained from patients with esophagectomy and esophagogastrostomy for ESCC. Western blot, immunohistochemistry and Quantitative RT-PCR were performed to evaluate protein and RNA expression levels of MTHFD1L. Knockdown of MTHFD1L expression was achieved by using short hairpin RNA. The effects of MTHFD1L silencing on ESCC cell proliferation and apoptosis were assessed by the MTT assay, Celigo assays, Annexin V FACS assay and Caspase-3/7 array in vitro. RESULTS: Twenty-three paired cancer and adjacent normal esophageal tissues from patients with ESCC were included in this study. MTHFD1L protein and RNA expression levels were significantly upregulated in ESCC tissue as compared with normal tissue. High expression of MTHFD1 was also detected in two esophageal cancer cell lines (TE-1 and EC109). Knockdown of MTHFD1L expression inhibited the proliferation of TE-1 cells, and the apoptosis was distinctly increased following shMTHFD1L infection. CONCLUSIONS: Our preliminary study highlighted for the first time that MTHFD1L might be involved in the development of ESCC, which may provide a new potential tumor-specific therapeutic targeting for anti-folate agents.

Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury.

BACKGROUND: Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a commonly used clinical immunonutrient, which has antioxidative and anti-inflammatory effects. However, the effects of ω-3 PUFA on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway are not clear. METHODS: The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway to evaluate the effects of ω-3 PUFA supplementation and gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. RESULTS: It was found that ω-3 PUFA supplementation inhibited TBI-induced microglial activation and expression of inflammatory factors (TNF-α, IL-1ß, IL-6, and IFN-γ), reduced brain edema, decreased neuronal apoptosis, and improved neurological functions after TBI. We further demonstrated that ω-3 PUFA supplementation inhibited HMGB1 nuclear translocation and secretion and decreased expression of HMGB1 in neurons and microglia in the lesioned areas. Moreover, ω-3 PUFA supplementation inhibited microglial activation and the subsequent inflammatory response by regulating HMGB1 and the TLR4/NF-κB signaling pathway. CONCLUSIONS: The results of this study suggest that microglial activation and the subsequent neuroinflammatory response as well as the related HMGB1/TLR4/NF-κB signaling pathway play essential roles in secondary injury after TBI. Furthermore, ω-3 PUFA supplementation inhibited TBI-induced microglial activation and the subsequent inflammatory response by regulating HMGB1 nuclear translocation and secretion and also HMGB1-mediated activation of the TLR4/NF-κB signaling pathway, leading to neuroprotective effects.