Hepatic arterial infusion chemotherapy, lenvatinib plus programmed cell death protein-1 inhibitors: A promising treatment approach for high-burden hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients. METHODS: We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths. CONCLUSION: The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.

Unclassified glutathione-S-transferase AiGSTu1 confers chlorantraniliprole tolerance in Agrotis ipsilon.

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.

Lenvatinib Plus PD-1 Inhibitors versus Regorafenib in Patients with Advanced Hepatocellular Carcinoma After the Failure of Sorafenib: A Retrospective Study.

Purpose: To evaluate the clinical outcomes of lenvatinib plus PD-1 inhibitors (LP) and regorafenib (R) in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure. Methods: From June 2018 to September 2021, 68 patients from a single center who received lenvatinib combined with PD-1 inhibitors or regorafenib after sorafenib treatment failure were analyzed. The tumor response and survival outcomes were compared between the LP group and R group. Prognostic factors for OS and PFS were determined using Cox proportional hazard regression models. Results: The ORR increased in the LP group (19.5% vs 7.4%, p =0.294), and the DCR was better in the R group (73.2% vs 44.4%, p =0.017). Additionally, median PFS and OS were not significantly different between the LP group and R two groups in survival analysis (PFS: 5.3 months vs 3.0 months, p =0.633; OS: 11.8 months vs 8.0 months, p =0.699). The common adverse events (≥grade 3) were hand-foot skin reactions (13.1%). In multivariate analyses, AFP≥400 ng/mL and ECOG PS 2 were independent risk factors for poor prognosis. Conclusion: The LP group appeared to have a trend of greater tumor response and a higher disease control rate than the R group among patients with sorafenib-resistant HCC, although PFS and OS did not differ significantly between the two groups.

Sonoelastography for Testicular Tumor Identification: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy.

The objective of this review was to summarize the applications of sonoelastography in testicular tumor identification and inquire about their test performances. Two authors independently searched English journal articles and full conference papers from CINAHL, Embase, IEEE Xplore®, PubMed, Scopus, and Web of Science from inception and organized them into a PIRO (patient, index test, reference test, outcome) framework. Eleven studies (n = 11) were eligible for data synthesis, nine of which (n = 9) utilized strain elastography and two (n = 2) employed shear-wave elastography. Meta-analyses were performed on the distinction between neoplasm (tumor) and non-neoplasm (non-tumor) from four study arms and between malignancy and benignity from seven study arms. The pooled sensitivity of classifying malignancy and benignity was 86.0% (95%CI, 79.7% to 90.6%). There was substantial heterogeneity in the classification of neoplasm and non-neoplasm and in the specificity of classifying malignancy and benignity, which could not be addressed by the subgroup analysis of sonoelastography techniques. Heterogeneity might be associated with the high risk of bias and applicability concern, including a wide spectrum of testicular pathologies and verification bias in the reference tests. Key technical obstacles in the index test were manual compression in strain elastography, qualitative observation of non-standardized color codes, and locating the Regions of Interest (ROI), in addition to decisions in feature extractions. Future research may focus on multiparametric sonoelastography using deep learning models and ensemble learning. A decision model on the benefits-risks of surgical exploration (reference test) could also be developed to direct the test-and-treat strategy for testicular tumors.

Diagnostic accuracy of circulating exosomal circRNAs in malignances: A meta-analysis and systematic review.

BACKGROUND: Pathogenesis of malignant tumors are often accompanied by aberrant expression of circular RNAs (circRNAs), indicating the potential diagnostic value of circRNAs in tumors. CircRNAs have been found to be enriched, stable and ubiquitous in serum and plasma exosomes. The study aims at evaluating the diagnostic performance of circulating (plasma and serum) exosomal circRNA in different types of cancer by synthesis of published data. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Medline and the Web of Science databases to identify potentially eligible studies published before April 2021. We conducted the meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. RESULTS: Eleven articles comprising 21 studies were included, and a total of 1609 cases and 1498 controls were evaluated. Six types of cancer were involved in these studies, including lung cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, multiple myeloma and osteosarcoma. The pooled sensitivity and specificity were 0.72 (95% confidence interval [CI], 0.62-0.81) and 0.83 (95% CI, 0.78-0.88), respectively. Summary receiver operating characteristic curve was constructed and the pooled value of area under curve was 0.86 (95% CI, 0.83-0.89), indicating a favorable diagnostic efficacy of circulating exosomal circRNAs in malignancies. CONCLUSIONS: In conclusion, our study evaluated the diagnostic power of circulating exosomal circRNAs in 6 types of cancer by synthesis of published data comprising 21 studies from eleven articles. The pooled analysis provided the evidence supporting circulating exosomal circRNAs as a promising noninvasive diagnostic biomarkers for malignancies.

Identification of 14 glutathione S-transferase genes from Lasioderma serricorne and characterization of LsGSTe1 involved in lambda-cyhalothrin detoxification.

In insects, glutathione S-transferases (GSTs) play a pivotal role in the detoxification of a wide range of pesticides. The cigarette beetle, Lasioderma serricorne, is an economically important pest insect of stored products. Recently, pyrethroid insecticides have been used to control this pest. However, little is known concerning the responses and functions of GSTs in L. serricorne under pyrethroid exposure. In this study, transcriptome sequencing was performed on L. serricorne, and a total of 14 GSTs were identified by retrieving the unigene dataset. Of these, 13 predicted GSTs fell into six cytosolic classes, namely, delta, epsilon, omega, sigma, theta, and zeta, and one was assigned to an "unclassified" group. The GST genes were differentially expressed in various larval tissues and at different developmental stages. Exposure to the pyrethroid insecticide lambda-cyhalothrin (LCT) caused oxidative stress in L. serricorne larvae and led to significantly elevated expression levels of six genes, among which LsGSTe1 was the most upregulated. Recombinant LsGSTE1 protein displayed LCT-metabolizing activity. Furthermore, LsGSTE1 protects cells against oxidative stress. Moreover, knockdown of LsGSTe1 by RNA interference dramatically increased the susceptibility of L. serricorne larvae to LCT treatment. The results from this study provide sequence resources and expression data for GST genes in L. serricorne. Our findings indicate that LsGSTE1 plays a dual role in LCT detoxification by metabolizing the pesticide and by preventing LCT-induced oxidative stress. Thus, the LsGSTe1 gene could be used as a potential target for sustainable management of the cigarette beetle.

Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy.

Previous studies suggest that baclofen may be useful in the treatment of intractable hiccup caused by chemotherapy. This study was aimed to assess the possible efficacy and safety of baclofen. In total, 65 patients with intractable hiccup caused by chemotherapy were screened. 45 patients with intractable hiccup caused by chemotherapy were finally recruited. Participants in the trial received 10 mg baclofen three times daily for 3 days. The primary outcome measure was cessation of hiccups. Secondary outcome measures included efficacy and adverse events. All 45 patients completed the study. Among them, 41 cases were cured (91.11%, 41/45), 4 cases were relieved (8.89%, 4/45), and the overall effective rate was 100% (45/45). Furthermore, the median remission time was 2(1, 9) times, the median cure time was 2(1, 9) times, the remission rate of one-time was 13.33% (6/45), the remission rate of two-time was 53.33% (24/45), and 2 cases (4.44%, 2/45) relapsed after drug withdrawal. No serious adverse events were documented. Only 1 case (2.22%) had grade 2 fatigue and 2 cases (4.44%) had grade 1 sleepiness. Baclofen is safe and effective in the treatment of intractable hiccup caused by chemotherapy of malignant tumor.

Endocrine Tumor Classification via Machine-Learning-Based Elastography: A Systematic Scoping Review.

Elastography complements traditional medical imaging modalities by mapping tissue stiffness to identify tumors in the endocrine system, and machine learning models can further improve diagnostic accuracy and reliability. Our objective in this review was to summarize the applications and performance of machine-learning-based elastography on the classification of endocrine tumors. Two authors independently searched electronic databases, including PubMed, Scopus, Web of Science, IEEEXpress, CINAHL, and EMBASE. Eleven (n = 11) articles were eligible for the review, of which eight (n = 8) focused on thyroid tumors and three (n = 3) considered pancreatic tumors. In all thyroid studies, the researchers used shear-wave ultrasound elastography, whereas the pancreas researchers applied strain elastography with endoscopy. Traditional machine learning approaches or the deep feature extractors were used to extract the predetermined features, followed by classifiers. The applied deep learning approaches included the convolutional neural network (CNN) and multilayer perceptron (MLP). Some researchers considered the mixed or sequential training of B-mode and elastographic ultrasound data or fusing data from different image segmentation techniques in machine learning models. All reviewed methods achieved an accuracy of ≥80%, but only three were ≥90% accurate. The most accurate thyroid classification (94.70%) was achieved by applying sequential training CNN; the most accurate pancreas classification (98.26%) was achieved using a CNN-long short-term memory (LSTM) model integrating elastography with B-mode and Doppler images.

Efficacy and Safety of Regorafenib with or without PD-1 Inhibitors as Second-Line Therapy for Advanced Hepatocellular Carcinoma in Real-World Clinical Practice.

Background: Regorafenib is the first oral targeted drug as a second-line agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib treatment. Recently, several studies demonstrated that the combination of regorafenib and PD-1 inhibitors showed a synergistic effect. Our study aimed to evaluate the efficacy of regorafenib with PD-1 inhibitors (RP) and regorafenib alone (R) as second-line treatment for advanced HCC. Methods: From October 2018 to January 2022, our retrospective study evaluated advanced HCC patients who received regorafenib with PD-1 inhibitors or regorafenib alone as a second-line treatment at the Second Affiliated Hospital of Nanchang University, China. The efficacy and safety were compared between RP and R groups. Results: In total, 78 patients were enrolled in our study and were separated into two groups - RP group (48) and R group (30) - according to the criteria. The ORR of RP group and R group was 18.8% and 10%, respectively, and the DCR was 66.7% and 43.3%, respectively. The RP group had a longer mPFS (5.9 months vs 3.0 months, P<0.001) and mOS (12.9 months vs 10.3 months, P=0.010) than the R group. Regorafenib monotherapy is an independent prognostic factor for OS and PFS. In OS, subgroup analysis showed that patients with AFP ≥ 400ng/mL, BCLC C stage and extrahepatic metastasis may benefit from RP, while in PFS, subgroup analysis showed that patients with BCLC C stage, AFP ≥ 400ng/mL, extrahepatic metastasis, ALBI ≥-2.60 and first-line treatment of sorafenib may benefit from RP. The incidence of grade 3/4 adverse reaction in the two groups was 22.9% and 23.3%, respectively, with no significant statistically difference (P=0.966). Conclusion: In the second-line therapy of advanced HCC, compared to regorafenib alone, the combination of regorafenib and PD-1 inhibitors showed promising efficacy and tolerable drug toxicity.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with programmed cell death protein-1 antibody and lenvatinib for advanced hepatocellular carcinoma.

Background: The purpose of the study was to assess the efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) who are undergoing hepatic arterial infusion chemotherapy (HAIC) combined with programmed cell death protein-1 (PD-1) antibody and lenvatinib. Methods: We retrospectively evaluated 61 patients treated with HAIC combined with PD-1 antibody and lenvatinib at the Second Affiliated Hospital of Nanchang University between September 2020 and January 2022 for advanced HCC. We analyzed tumor response, progression free survival (PFS), and treatment-related adverse events (TRAEs). Results: The objective response rate (ORR) was 36.1% (RECIST 1.1)/57.4% (mRECIST) and the disease control rate (DCR) was 82.0%. The overall median PFS was 6.0 months, 6.7 months for first-line treatment, and 4.3 months for second-line treatment. The most common TRAEs were neutropenia (50.8%), abdominal pain (45.9%), and aspartate aminotransferase increase (39.3%). Conclusion: Hepatic arterial infusion chemotherapy combined with PD-1 antibody and lenvatinib is effective in the treatment of advanced HCC, and the TRAEs are generally controllable.

PD-1 inhibitors plus lenvatinib versus PD-1 inhibitors plus regorafenib in patients with advanced hepatocellular carcinoma after failure of sorafenib.

Background: Lenvatinib, regorafenib and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising clinical outcomes in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure, respectively. However, the combination of the two treatments has not been reported. We compared the efficacy of PD-1 inhibitors with lenvatinib (PL) and PD-1 inhibitors plus regorafenib (PR) in patients with advanced HCC in this study. Methods: We conducted a retrospective study of advanced HCC patients who undergone PD-1 inhibitors combined with lenvatinib or regorafenib after failure of sorafenib at Second Affiliated Hospital of Nanchang University from July 2018 and December 2020. The overall survival (OS), progression-free survival (PFS), effective rates and treatment-related adverse events (TRAEs) were investigated. Results: In total, 61 patients met the criteria and were included in the present study, and they were divided into the PL group (n = 32) and PR group (n = 29). The overall response rate (ORR) (12.5%vs. 10.3%, respectively; p = 0.557) and disease control rate (DCR) (71.9%vs. 58.6%, respectively; p < 0.207) were higher in the PL group than in the PR group, but there was no statistical difference.Furthermore, median PFS and OS were not significantly different between the two groups in Kaplan-Meier survival analysis (PFS: 5.3 months vs 4.0 months, p = 0.512; OS: 14.1 months vs 13.7 months, p = 0.764 for the PL group vs PR group). The most common treatment-related adverse events (TRAEs) were hand -foot skin reaction (24/61,39.3%), hypertension (20/61,32.8%) and hypothyroidism (13/61,21.3%). The frequent TRAEs (≥Grade 3) during PD-1 inhibitors plus lenvatinib or regorafenib treatment were hand-foot skin reaction (5/29,12.4%), thrombocytopenia (2/29 6.90%) and proteinuria (n =2/32,6.25%). Conclusions: Combination of lenvatinib/regorafenib and PD-1 inhibitors is a promising therapy for HCC patients after sorafenib failure.

Nerve root magnetic stimulation improves locomotor function following spinal cord injury with electrophysiological improvements and cortical synaptic reconstruction.

Following a spinal cord injury, there are usually a number of neural pathways that remain intact in the spinal cord. These residual nerve fibers are important, as they could be used to reconstruct the neural circuits that enable motor function. Our group previously designed a novel magnetic stimulation protocol, targeting the motor cortex and the spinal nerve roots, that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury. Here, we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury. Rats underwent surgery to clamp the spinal cord at T10; three days later, the rats were treated with repetitive magnetic stimulation (5 Hz, 25 pulses/train, 20 pulse trains) targeting the nerve roots at the L5-L6 vertebrae. The treatment was repeated five times a week over a period of three weeks. We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord. In addition, the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex. Overall, the results suggest that nerve root magnetic stimulation may be an effective, noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.

Breast Tumour Classification Using Ultrasound Elastography with Machine Learning: A Systematic Scoping Review.

Ultrasound elastography can quantify stiffness distribution of tissue lesions and complements conventional B-mode ultrasound for breast cancer screening. Recently, the development of computer-aided diagnosis has improved the reliability of the system, whilst the inception of machine learning, such as deep learning, has further extended its power by facilitating automated segmentation and tumour classification. The objective of this review was to summarize application of the machine learning model to ultrasound elastography systems for breast tumour classification. Review databases included PubMed, Web of Science, CINAHL, and EMBASE. Thirteen (n = 13) articles were eligible for review. Shear-wave elastography was investigated in six articles, whereas seven studies focused on strain elastography (5 freehand and 2 Acoustic Radiation Force). Traditional computer vision workflow was common in strain elastography with separated image segmentation, feature extraction, and classifier functions using different algorithm-based methods, neural networks or support vector machines (SVM). Shear-wave elastography often adopts the deep learning model, convolutional neural network (CNN), that integrates functional tasks. All of the reviewed articles achieved sensitivity ³ 80%, while only half of them attained acceptable specificity ³ 95%. Deep learning models did not necessarily perform better than traditional computer vision workflow. Nevertheless, there were inconsistencies and insufficiencies in reporting and calculation, such as the testing dataset, cross-validation, and methods to avoid overfitting. Most of the studies did not report loss or hyperparameters. Future studies may consider using the deep network with an attention layer to locate the targeted object automatically and online training to facilitate efficient re-training for sequential data.

Efficacy and Safety of Fruquintinib Plus PD-1 Inhibitors Versus Regorafenib Plus PD-1 Inhibitors in Refractory Microsatellite Stable Metastatic Colorectal Cancer.

BACKGROUND: Microsatellite stability (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. Studies have shown that antiangiogenic drugs combined with programmed death receptor-1 (PD-1) inhibitors can improve immunosuppression. The purpose of this study was to compare the efficacy of fruquintinib combined with PD-1 inhibitor (FP) and regorafenib combined with PD-1 inhibitor (RP) in the treatment of advanced mCRC with MSS or pMMR. MATERIALS AND METHODS: We retrospectively collected advanced MSS or pMMR mCRC patient data from The Second Affiliated Hospital of Nanchang, China, from June 2019 to March 2021. Then, we analyzed and compared the efficacy and safety of FP and RP. RESULTS: A total of 51 patients who met the criteria were divided into FP (n = 28) and RP groups (n = 23). The overall response rate of the FP and RP groups was 7.1% and 8.7% and the disease control rate was 89.3% and 56.5%, respectively. The median progression-free survival (PFS) time was higher in the FP group than in the RP group (6.4 vs. 3.9 months, respectively; P = 0.0209). Patients with no liver metastasis, KRAS wild type, and left colon tumor may benefit from FP. Eight patients (15.7%) had grade 3 toxicity related to treatment. Cox multivariate regression analysis showed that the treatment method was an independent risk factor for median PFS time. CONCLUSION: Our study indicates that FP could improve PFS time of patients with advanced mCRC compared with RP.

Identification and Expression Profiles of 14 Odorant-Binding Protein Genes From Pieris rapae (Lepidoptera: Pieridae).

The small white butterfly, Pieris rapae (L.), is an important insect pest of Brassica crops. This species utilize olfactory cues to find their hosts and mates. However, the molecular mechanism underlying the olfactory perception in this species remains unclear. Here, we identified 14 odorant-binding proteins (OBP) genes-essential for insect olfaction-in P. rapae by exploring a previously published transcriptome dataset. Proteins encoded by all of these genes contain N-terminal signal peptides and six positionally conserved cysteine residues, which are characteristic of insect OBPs. These OBPs displayed high amino acid identity with their respective orthologs in other lepidopterans, and several conserved motifs were identified within these OBPs. Phylogenetic analysis showed that these OBPs were well segregated from each other and clustered into different branches. PrapOBP1 and PrapOBP2 were clustered into the 'general odorant-binding protein' clade, and PrapOBP3 and PrapOBP4 fall into the 'pheromone-binding protein' clade. The 14 OBP genes were located on seven genomic scaffolds. Of these, PrapOBP1, 2, 3, and 4 were located on scaffold332, whereas PrapOBP5, 6, 7, 8, and 9 were located on scaffold116. Ten of the 14 genes had antenna-biased expression. Of these, PrapOBP1, 2, 4, and 13 were enriched in male antennae, whereas PrapOBP7 and PrapOBP10 were female-biased. Our findings suggest that these OBPs may be involved in olfactory communication. To the best of our knowledge, this is the first report on the identification and characterization of OBPs in P. rapae, and our findings provide a solid foundation for studying the functions of these genes.

Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation.

Spinal cord injury is linked to the interruption of neural pathways, which results in irreversible neural dysfunction. Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury, which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies. Besides the involvement of endogenous stem cells in neurogenesis and neural repair, exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases. However, to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury, appropriate interventional measures (e.g., neuromodulation) should be adopted. Neuromodulation techniques, such as noninvasive magnetic stimulation and electrical stimulation, have been safely applied in many neuropsychiatric diseases. There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system; namely, by exciting, inhibiting, or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury. Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth, encourages the formation of new synaptic connections to promote neural plasticity, and improves motor function recovery in patients with spinal cord injury. With the development of biomaterial technology and biomechanical engineering, several emerging treatments have been developed, such as robots, brain-computer interfaces, and nanomaterials. These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury. However, large-scale clinical trials need to be conducted to validate their efficacy. This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence, to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.

Characterization of the active fragments of Spodoptera litura Lebocin-1.

Insects can produce various antimicrobial peptides (AMPs) upon immune stimulation. One class of AMPs are characterized by their high proline content in certain fragments. They are generally called proline-rich antimicrobial peptides (PrAMPs). We previously reported the characterization of Spodoptera litura lebocin-1 (SlLeb-1), a PrAMP proprotein. Preliminary studies with synthetic polypeptides showed that among the four deductive active fragments, the C-terminal fragment SlLeb-1 (124-158) showed strong antibacterial activities. Here, we further characterized the antibacterial and antifungal activities of 124-158 and its four subfragments: 124-155, 124-149, 127-158, and 135-158. Only 124-158 and 127-158 could agglutinate bacteria, while 124-158 and four subfragments all could agglutinate Beauveria bassiana spores. Confocal microscopy showed that fluorescent peptides were located on the microbial surface. Fragment 135-158 lost activity completely against Escherichia coli and Staphylococcus aureus, and partially against Bacillus subtilis. Only 124-149 showed low activity against Serratia marcescens. Negative staining, transmission, and scanning electron microscopy of 124-158 treated bacteria showed different morphologies. Flow cytometry analysis of S. aureus showed that 124-158 and four subfragments changed bacterial subpopulations and caused an increase of DNA content. These results indicate that active fragments of SlLeb-1 may have diverse antimicrobial effects against different microbes. This study may provide an insight into the development of novel antimicrobial agents.

Nicotine exerts neuroprotective effects by attenuating local inflammatory cytokine production following crush injury to rat sciatic nerves.

Recent studies have demonstrated that nicotine exhibited anti-inflammatory and neuroprotective properties by interacting with the alpha 7 nicotinic acetylcholine receptor (α7nAChR). However, the role of nicotine in regeneration during peripheral nerve injury has not been elucidated. The aim of this study was to investigate whether nicotine down-regulated production of proinflammatory cytokines and promoted peripheral nerve regeneration in rats. Rats challenged with sciatic nerve crush injury were treated with nicotine (1.5 mg/kg), three times per day. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL-1ß), pinch test results, growth-associated protein 43 (GAP-43) expression, morphometric analyses, and the sciatic functional indexes were determined in sciatic nerves. Treatment with nicotine decreased local levels of TNF-α and IL-1ß, and increased the expression of GAP-43. Nicotine also improved nerve regeneration and functional recovery. The overall protective effects of nicotine were reversed by concomitant treatment with α7nACHR antagonist methyllycaconitine, indicating that nicotine exerted its specific anti-inflammatory and neuroprotective effects through the α7nAChR. These findings show that nicotine administration can provide a potential therapeutic pathway for the treatment of peripheral nerve injury, by a direct protective effect through the α7nAChR-mediated cholinergic anti-inflammatory pathway.

LINC00152 promotes the proliferation of gastric cancer cells by regulating B-cell lymphoma-2.

LINC00152 has been considered to be associated with the tumorigenesis and the occurrence of gastric cancer; however, the mechanism of LINC00152 has yet to be fully elucidated. In the present study, the expression levels of LINC00152 in tissues, serum, and peripheral blood mononuclear cells (PBMCs) of patients with gastric cancer were determined using real-time polymerase chain reaction. The functions of LINC00152 with respect to the proliferation, apoptosis, migration, and invasive abilities of the gastric cancer cells were evaluated by cell proliferation analysis, flow cytometry, cell scratch wound assay, and transwell migration experiments. A mouse xenotransplant model of gastric tumors was established to detect the role of LINC00152 in vivo, and the expression levels of B-cell lymphoma-2 (Bcl-2) family proteins were investigated by Western blot analysis. The results revealed that LINC00152 was overexpressed in tissues, serum, and PBMCs of patients with gastric cancer. Moreover, LINC00152 could promote the migration and invasive abilities and suppress the apoptosis, of gastric cancer cells through regulating the Bcl-2 protein family. LINC00152 could bind with Bcl-2 directly to induce the activation of cell cycle signaling, and this may be a potential target for the therapy of gastric cancer in the future.

Association between dietary protein intake and prostate cancer risk: evidence from a meta-analysis.

BACKGROUND: Many studies were conducted to explore the relationship between dietary protein intake and risk of prostate cancer, obtaining inconsistent results. Therefore, this study aims to comprehensively explore the predicted role of dietary protein intake for risk of prostate cancer. METHODS: Databases of Web of Knowledge, PubMed, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang Med Online were searched up to August 30, 2017. Eligible studies were included based on our definite inclusion criteria. Summarized relative risk (RR) and corresponding 95% confidence interval (CI) were pooled with a random effects model. Sensitive analysis and publication bias were performed. RESULTS: At the end, a total of 12 articles comprising 13,483 prostate cancer cases and 286,245 participants were included. The summary RR and 95%CI of the highest protein intake compared to those with the lowest protein intake on prostate cancer risk were 0.993 (95%CI = 0.930-1.061), with no between-study heterogeneity found (I2 = 0.0%, P = 0.656). Moreover, the association was not significant on prostate cancer risk with animal protein intake [RR = 1.001, 95%CI = 0.917-1.092] or vegetable protein intake [RR = 0.986, 95%CI = 0.904-1.076]. The results were not changed when we conducted subgroup analysis by study design, cancer type, or geographic locations. We did not detect any publication bias using Egger's test (P = 0.296) and funnel plot. CONCLUSION: Our study concluded that protein intake may be not associated on prostate cancer.