Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis.

Diallyl trisulfide (DATS), an organosulfide compound derived from garlic, is renowned for its potent antioxidant properties, particularly in countering the generation of reactive oxygen species (ROS). It has also gained recognition as a potential agent for preventing heart-related conditions. Doxorubicin (Dox), a commonly used chemotherapeutic drug, is known to induce severe cardiac complications by promoting ROS production. Therefore, it was imperative to investigate whether DATS possesses cardioprotective capabilities against Dox-induced cardiac apoptosis and elucidate the underlying mechanisms. In this study, we observed that the intracellular ROS levels and cardiac apoptosis were heightened in H9c2 cells exposed to Dox (1 µM). However, treatment with 10 µM DATS effectively mitigated the Dox-induced ROS generation and apoptotic signaling, concurrently activating the PI3K/Akt pathway. Notably, the anti-apoptotic effects of DATS were attenuated when PI3K siRNA and the LY294002 PI3K inhibitor were employed. Furthermore, the TUNEL assay results demonstrated a significant reduction in Dox-induced apoptosis with DATS treatment. In summary, our findings indicate that DATS can activate the PI3K/Akt pathway, reducing ROS production in cardiac cells exposed to Dox, and subsequently rescue cardiac cells from apoptosis.

Association between new plasma inflammatory markers and risk of colorectal neoplasms in individuals over 50 years old.

OBJECTIVE(S): The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer. METHOD: The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2-T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared. RESULT(S): Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old. CONCLUSION(S): Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma.

Bacterial and Fungal Biocontrol Agents for Plant Disease Protection: Journey from Lab to Field, Current Status, Challenges, and Global Perspectives.

Plants are constantly exposed to various phytopathogens such as fungi, Oomycetes, nematodes, bacteria, and viruses. These pathogens can significantly reduce the productivity of important crops worldwide, with annual crop yield losses ranging from 20% to 40% caused by various pathogenic diseases. While the use of chemical pesticides has been effective at controlling multiple diseases in major crops, excessive use of synthetic chemicals has detrimental effects on the environment and human health, which discourages pesticide application in the agriculture sector. As a result, researchers worldwide have shifted their focus towards alternative eco-friendly strategies to prevent plant diseases. Biocontrol of phytopathogens is a less toxic and safer method that reduces the severity of various crop diseases. A variety of biological control agents (BCAs) are available for use, but further research is needed to identify potential microbes and their natural products with a broad-spectrum antagonistic activity to control crop diseases. This review aims to highlight the importance of biocontrol strategies for managing crop diseases. Furthermore, the role of beneficial microbes in controlling plant diseases and the current status of their biocontrol mechanisms will be summarized. The review will also cover the challenges and the need for the future development of biocontrol methods to ensure efficient crop disease management for sustainable agriculture.

Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant.

Introduction: Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective. Methods: We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness of WKS13 was evaluated in a hamster model. Results: Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant. Conclusions: Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.

Transiently impaired endothelial function during thyroid hormone withdrawal in differentiated thyroid cancer patients.

Purpose: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. Methods: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. Results: We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD(P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Conclusion: Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy.

DSC2 suppresses the growth of gastric cancer through the inhibition of nuclear translocation of γ-catenin and PTEN/PI3K/AKT signaling pathway.

BACKGROUND: Globally, gastric cancer (GC) is still a major leading cause of cancer-associated deaths. Downregulated desmocollin2 (DSC2) is considered to be closely related to tumor progression. However, the underlying mechanisms of DSC2 in GC progression require further exploration. METHOD: We initially constructed different GC cells based on DSC2 contents, established the mouse tumor xenografts, and subsequently performed clonal formation, MTT, Caspase-3 activity, and sperm DNA fragmentation assays to detect the functions of DSC2 in GC growth. Subsequently, we performed western blot, Co-IP, and immunofluorescence assays to investigate the underlying mechanisms through pretreatment with PI3K inhibitor, LY294002, and its activator, recombinant human insulin-like growth factor I (IGF1). RESULT: DSC2 could significantly inhibit the viability of GC cells at both in vitro and in vivo levels. The underlying mechanism may be that DSC2 binds the γ-catenin to decrease its nuclear level, thereby downregulating the anti-apoptotic factor BCL-2 expression and upregulating the pro-apoptotic factor P53 expression, which adjusts the PTEN/PI3K/AKT signaling pathway to promote the cancer cell apoptosis. CONCLUSIONS: Our finding suggests that DSC2 might be a potential therapeutic target for the treatment of cancers, most especially GC.

Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation.

Neutralising monoclonal antibody (mAb) is an important weapon in our arsenal for combating respiratory viral infections. However, the effectiveness of neutralising mAb has been impeded by the rapid emergence of mutant variants. Early administration of broad-spectrum mAb with improved delivery efficiency can potentially enhance efficacy and patient outcomes. WKS13 is a humanised mAb which was previously demonstrated to exhibit broad-spectrum activity against SARS-CoV-2 variants. In this study, a dual targeting formulation strategy was designed to deliver WKS13 to both the nasal cavity and lower airways, the two critical sites of infection caused by SARS-CoV-2. Dry powders of WKS13 were first prepared by spray drying, with cyclodextrin used as stabiliser excipient. Two-fluid nozzle (TFN) was used to produce particles below 5 µm for lung deposition (C-TFN formulation) and ultrasonic nozzle (USN) was used to produce particles above 10 µm for nasal deposition (C-USN formulation). Gel electrophoresis and size exclusion chromatography studies showed that the structural integrity of mAb was successfully preserved with no sign of aggregation after spray drying. To achieve dual targeting property, C-TFN and C-USN were mixed at various ratios. The aerosolisation property of the mixed formulations dispersed from a nasal powder device was examined using a Next Generation Impactor (NGI) coupled with a glass expansion chamber. When the ratio of C-TFN in the mixed formulation increased, the fraction of particles deposited in the lung increased proportionally while the fraction of particles deposited in the nasal cavity decreased correspondingly. A customisable aerosol deposition profile could therefore be achieved by manipulating the mixing ratio between C-TFN and C-USN. Dual administration of C-TFN and C-USN powders to the lung and nasal cavity of hamsters, respectively, was effective in offering prophylactic protection against SARS-CoV-2 Delta variant. Viral loads in both the lung tissues and nasal wash were significantly reduced, and the efficacy was comparable to systemic administration of unformulated WKS13. Overall, dual targeting powder formulation of neutralising mAb is a promising approach for prophylaxis of respiratory viral infections. The ease and non-invasive administration of dual targeting nasal powder may facilitate the widespread distribution of neutralising mAb during the early stage of unpredictable outbreaks.

Meloidogyne graminicola Population Structure in China Suggests a South-to-North Expansion.

The distribution range of root-knot nematode Meloidogyne graminicola is rapidly expanding, posing a severe threat to rice production. In this study, the sequences of cytochrome oxidase subunit I (COI) genes of rice M. graminicola populations from all reported provinces in China were amplified and sequenced by PCR. The distribution pattern and phylogenetic tree showed that all 54 M. graminicola populations in China have distinct geographical distribution characteristics; specifically, cluster 1 (southern China), cluster 2 (central south and southwest China), and cluster 3 (central and eastern China). The high haplotype diversity (Hd = 0.646) and low nucleotide diversity (π = 0.00682), combined with the negative value of Tajima's D (-1.252) and Fu's Fs (-3.06764), suggested that all nematode populations were expanding. The existence of high genetic differentiation (Fst = 0.5933) and low gene flow (Nm = 0.3333) indicated that there was a block of gene exchange between most populations. Mutation accumulation with population expansion might be directly responsible for the high genetic differentiation; therefore, the tested nematode population showed high within-group genetic variation (96.30%). The haplotype Hap8 was located at the bottom of the network topology, with the widest distribution and the highest frequency (59.26%), indicating that it was the ancestral haplotype. The populations in cluster 3 were newly invasive according to the lowest frequency of occurrence of Hap8, the highest number of endemic haplotypes, and the highest total haplotype frequency (60%). In contrast, cluster 1 having the highest genetic diversity (Hd = 0.772, π = 0.01127) indicated that it was the most primitive. Interestingly, the highest gene flow (Nm > 1), lowest genetic differentiation (Fst ≤ 0.33), and closest genetic distance (0.000) only occurred between the Guangdong/Hainan population and others, which suggested that there might be channels for gene exchange between them and that long-distance dispersal occurred. This suggestion is further confirmed by the weak correlation between genetic distance and geographical distance. Based on these data, a hypothesis can be drawn that M. graminicola populations in China were spreading from south to north, specifically from Guangdong and Hainan Provinces to other regions. Natural selection (including anthropogenic) and genetic drift were the main drivers of their evolution. Coincidentally, this hypothesis was consistent with the gradual warming trend and the chronological order of reporting these populations. The main factors influencing current M. graminicola population expansion and distribution patterns might be geography, climate, long-distance seedling transport, interregional operations of agricultural machinery, and rotation mode. It reminds human beings of the necessity to be vigilant about preventing nematode disease according to local conditions all year round.

Variable Neighborhood Search for Multi-Cycle Medical Waste Recycling Vehicle Routing Problem with Time Windows.

BACKGROUND: Improper disposal of urban medical waste is likely to cause a series of neglective impacts. Therefore, we have to consider how to improve the efficiency of urban medical waste recycling and lowering carbon emissions when facing disposal. METHODS: This paper considers the multi-cycle medical waste recycling vehicle routing problem with time windows for preventing and reducing the risk of medical waste transportation. First, a mixed-integer linear programming model is formulated to minimize the total cost consisting of the vehicle dispatch cost and the transportation costs. In addition, an improved neighborhood search algorithm is designed for handling large-sized problems. In the algorithm, the initial solution is constructed using the Clarke-Wright algorithm in the first stage, and the variable neighborhood search algorithm with a simulated annealing strategy is introduced for exploring a better solution in the second stage. RESULTS: The computational results demonstrate the performance of the suggested algorithm. In addition, the total cost of recycling in the periodic strategy is lower than with the single-cycle strategy. CONCLUSIONS: The proposed model and algorithm have the management improvement value of the studied medical waste recycling vehicle routing problem.

Long noncoding RNA DLEU2 promotes growth and invasion of hepatocellular carcinoma by regulating miR-30a-5p/PTP4A1 axis.

Increasing data indicate that long noncoding RNA (lncRNA) DLEU2 is implicated in carcinogenesis in multiple malignancies including hepatocellular carcinoma (HCC). However, the role and molecular mechanism by which lncRNA DLEU2 contributes to HCC remain unknown. The association of lncRNA DLEU2 with clinicopathological characteristics and prognosis in patients with HCC was analyzed by qRT-PCR, and public TCGA dataset. CCK-8, colony formation and Transwell assays were performed to verify the role of lncRNA DLEU2 in HCC. RNA immunoprecipitation (RIP), luciferase gene report and qRT-PCR assays were employed to uncover lncRNA DLEU2-spevific binding with miR-30a-5p. The effect of lncRNA DLEU2 and (or) miR-30a-5p on PTP4A1 expression was examined by Western blot analysis. As a consequence, we found that lncRNA DLEU2 was upregulated in HCC tissue samples and associated with distant metastasis and poor survival in patients with HCC. Knockdown of lncRNA DLEU2 impaired HCC cell proliferation, colony formation and invasion, but ectopic expression of lncRNA DLEU2 abolished these effects. Furthermore, lncRNA DLEU2 harbored a negative correlation and specific binding with miR-30a-5p in HCC cells. Knockdown of lncRNA DLEU2 upregulated miR-30a-5p, but downregulated its target PTP4A1, and miR-30a-5p abrogated lncRNA DLEU2-induced tumor-promoting effects and PTP4A1 upregulation. Taken together, our findings demonstrate that lncRNA DLEU2 promotes growth and invasion of HCC cells by regulating miR-30a-5p/ PTP4A1 axis.

CD137 Costimulation Enhances the Antitumor Activity of Vγ9Vδ2-T Cells in IL-10-Mediated Immunosuppressive Tumor Microenvironment.

Although γδ-T cell-based tumor immunotherapy using phosphoantigens to boost γδ-T cell immunity has shown success in some cancer patients, the clinical application is limited due to the rapid exhaustion of Vγ9Vδ2-T cells caused by repetitive stimulation from phosphoantigens and the profoundly immunosuppressive tumor microenvironment (TME). In this study, using a cell culture medium containing human and viral interleukin-10 (hIL-10 and vIL-10) secreted from EBV-transformed lymphoblastoid B cell lines (EBV-LCL) to mimic the immunosuppressive TEM, we found that the antitumor activity of Vγ9Vδ2-T cells was highly suppressed by endogenous hIL-10 and vIL-10 within the TME. CD137 costimulation could provide an anti-exhaustion signal to mitigate the suppressive effects of IL-10 in TME by suppressing IL-10R1 expression on Vγ9Vδ2-T cells. CD137 costimulation also improved the compromised antitumor activity of Vγ9Vδ2-T cells in TME with high levels of IL-10 in Rag2-/- γc-/- mice. In humanized mice, CD137 costimulation boosted the therapeutic effects of aminobisphosphonate pamidronate against EBV-induced lymphoma. Our study offers a novel approach to overcoming the obstacle of the hIL-10 and vIL-10-mediated immunosuppressive microenvironment by costimulating CD137 and enhancing the efficacy of γδ-T cell-based tumor therapy.

[Preparation and identification of neutralizing antibodies to envelope protein domain III(ED III) of the four dengue virus serotypes].

Objective To prepare neutralizing monoclonal antibodies (mAbs) against envelope protein domain III of the four dengue virus serotypes (DENV-EDIII) and identify its specificity. Methods BALB/c mice were immunized with recombinant EDIII protein (rDENV-EDIII) of the four DENV serotypes. Hybridoma cells secreting DENV-EDIII antibodies were screened by indirect ELISA. The specificity of positive hybridoma cells were further tested by indirect immunofluorescence assay (IFA). The neutralizing activities of DENV-EDIII mAbs in vitro were determined by the enzyme-linked immunospot microneutralization test (ELISPOT-MNT). Results 6 mAbs specific for the EDIII of the four DENV serotypes and 11 mAbs specific for only one serotype of DENV-EDIII protein were obtained, of which one monoclonal antibody had a balanced strong neutralizing activity against the four DENV serotypes in vitro, and its 50% inhibitory concentrations (IC50) for the four DENV serotypes was 0.05 µg/mL, 1.89 µg/mL, 0.02 µg/mL, 3.91 µg/mL, respectively. Conclusion A specific monoclonal antibody against DENV-EDIII is successfully screened and obtained to neutralize the four DENV serotypes.

Critical Phenomena in Dynamical Scalarization of Charged Black Holes.

We report a new black hole (BH) scalarization mechanism and disclose novel dynamical critical phenomena in the process of the nonlinear accretion of the scalar field into BHs. The accretion process can transform a seed BH into a final scalarized or bald BH, depending on the initial parameter of the scalar field p. There is a critical parameter p_{*} and near it all intermediate solutions are attracted to a critical solution (CS) and stay there for a time scaling as T∝-γln|p-p_{*}|. At late times, the solutions evolve into scalarized black holes (BHs) if p>p_{*}, or bald BHs if p

High-specificity targets in SARS-CoV-2 N protein for serological detection and distinction from SARS-CoV.

Numerous serological detection kits are being rapidly developed and approved for screening and diagnosing suspected coronavirus disease 2019 (COVID-19) cases. However, cross-reactivity between pre-existing antibodies against other coronaviruses and the captured antigens in these kits can affect detection accuracy, emphasizing the necessity for identifying highly specific antigen fragments for antibody detection. Thus, we performed a conservation and specificity analysis of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein. We also integrated various B-cell epitope prediction methods to obtain possible dominant epitope regions for the N protein, analyzed the differences in serological antibody levels for different epitopes using ELISA, and identified N protein epitopes for IgG and IgM with high-specificity. The SARS-CoV-2 N protein showed low mutation rates and shared the highest amino acid similarity with SARS-CoV; however, it differed substantially from other coronaviruses. Tests targeting the SARS-CoV-2 N protein produce strong positive results in patients recovering from SARS-CoV. The N18-39 and N183-197 epitopes for IgG and IgM detection, respectively, can effectively overcome cross-reactivity, and even exhibit good specificity between SARS-CoV-2 and SARS-CoV. The antibody levels detected with these were consistent with those detected using the complete N protein. These findings provide a basis for serological diagnosis and determining the kinetics of SARS-CoV-2 antibody detection in patients.

Low-frequency ultrasound combined with microbubbles improves gene transfection in prostate cancer cells in vitro and in vivo.

OBJECTIVES: The aim of this study is to explore whether low-frequency ultrasound combined with microbubbles improves pEGFP genes transfection into human prostate cancer cells. METHODS: Ultrasound with frequency of 80 kHz and duty cycle of 50% was adopted in the study; in in vitro experiments, cell lysis, and membrane damage were evaluated after ultrasound exposure; and the membrane continuity and transfection efficiency were observed by transmission electron microscope and laser scanner, respectively. Human prostate cancer xenograft models were exposed to ultrasound and transfection efficiency and histological examination were analyzed. RESULTS: Compared with the control group, ultrasound combined with microbubbles significantly improves gene transfection efficiency (P < .05). In in vitro study, ultrasound combined with microbubbles resulted in cell lysis and the interruption of cell membrane continuity, and its average transfection efficiency was 9.9%; the green fluorescence intensity was 15.2% in the ultrasound combined with microbubbles group in vivo; both values were higher than that in the control group (P < .05). CONCLUSION: Low-frequency ultrasound combined with microbubbles could be used as a method to promote gene transfection in prostate cancer cells.

AIM2 inhibits the proliferation, invasion and migration, and promotes the apoptosis of osteosarcoma cells by inactivating the PI3K/AKT/mTOR signaling pathway.

Osteosarcoma is a primary bone tumor that mainly occurs in children and adolescents. Absent in melanoma 2 (AIM2) has been demonstrated to be involved in regulating the occurrence and development of cancer, exerting oncogenic and pro­cancer effects; however, its role in osteosarcoma is poorly understood. The present study aimed to explore the function and molecular mechanism of AIM2 in the progression of osteosarcoma. In the present study, AIM2 expression was predicted using the Cancer Cell Line Encyclopedia database and examined in several osteosarcoma cell lines using reverse transcription­quantitative PCR and western blotting. Following AIM2 overexpression, cell proliferation and apoptosis were examined using Cell Counting Kit­8, colony formation and TUNEL staining assays. The expression levels of proteins related to apoptosis, epithelial­mesenchymal transition (EMT) and the PI3K/AKT/mTOR signaling pathway were determined by western blotting. Additionally, cell invasion and migration were assessed using Transwell and wound healing assays. After addition of the PI3K/AKT/mTOR signaling pathway inhibitor LY294002 or activator 740Y­P, cell function analysis was performed. The results demonstrated that AIM2 was expressed at low levels in osteosarcoma cell lines. AIM2 overexpression inhibited proliferation, invasion, migration and EMT, and promoted apoptosis in osteosarcoma cells. Furthermore, the levels of phosphorylated (p)­PI3K, p­AKT and p­mTOR were markedly downregulated following AIM2 overexpression. Furthermore, LY294002 treatment had the same effects as AIM2 upregulation on osteosarcoma cell proliferation, apoptosis, invasion, migration and EMT. By contrast, 740Y­P reversed the effects of AIM2 overexpression on the behavior of osteosarcoma cells. Overall, the findings of the present study demonstrated that AIM2 may inhibit the progression of osteosarcoma by inactivating the PI3K/AKT/mTOR signaling pathway, and suggested that AIM2 may be a promising marker for the treatment of osteosarcoma.

Predictive value and regulatory mechanism of serum miR-499a-5p on myocardial dysfunction in sepsis.

BACKGROUND: This study sought to investigate the predictive value and regulatory mechanism of serum miR-499a-5p in sepsis-induced myocardial dysfunction (SIMD). METHODS: A total of 60 patients with sepsis and 60 healthy volunteers were enrolled in this study. The serum levels of miRNAs (miR-451, miR-378 and miR-499a-5p) were detected. Receiver operating characteristic curve and logistic regression analysis were used to evaluate the diagnostic and prognostic value of miR-499a-5p in SIMD patients. AC16 cells were used to establish SIMD model in vitro using lipopolysaccharide (LPS). An analysis was conducted for miR-499a-5p expression, cell viability, and the concentration of creatine kinase-MB isoform (CK-MB), brain natriuretic peptide (BNP), superoxide dismutase (SOD) and cytochrome C oxidase IV (COX IV). The downstream target of miR-499a-5p was verified. RESULTS: Our results revealed a poor expression of miR-499a-5p in the serum of SIMD patients, while no significant difference was evident for miR-451 and miR-378. The level of miR-499a-5p in the survival group was higher than the non-survival group. miR-499a-5p elicited good diagnostic and prognostic value for SIMD. Our findings revealed that miR-499a-5p was decreased significantly in LPS-treated cardiomyocytes. After overexpression of miR-499a-5p, the cell viability increased, and the concentrations of CK-MB and BNP were decreased, while the concentrations of SOD and COX IV were increased. EIF4E was validated as the target of miR-499a-5p. After overexpression of EIF4E, the cell viability was decreased and the concentrations of CK-MB and BNP were increased while the concentrations of SOD and COX IV were decreased. CONCLUSION: The level of miR-499a-5p is weak in SIMD patients. miR-499a-5p has a good diagnostic and prognostic value for SIMD by inhibiting EIF4E transcription.

Delayed diagnosis of ascending colon mucinous adenocarcinoma with local abscess as primary manifestation: Report of three cases.

BACKGROUND: Colorectal mucinous adenocarcinoma is a distinct subtype of colorectal adenocarcinoma that is not sensitive to chemotherapy and radiotherapy, and its prognosis is worse than that of nonmucinous adenocarcinoma. Early diagnosis and aggressive surgical treatment may be the key to improving the prognosis of patients. Ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess caused by non-intestinal perforation has never been reported. Moreover, since the lumen of the ascending colon is large, and early stage ascending colon cancer lacks typical clinical manifestations, the diagnosis may be delayed easily. We herein report three cases of delayed diagnosis of colorectal mucinous adenocarcinoma. CASE SUMMARY: We present three patients (two females and one male) with mucinous ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess (the right area of the lumbar spine, right groin, and lower right abdomen) caused by non-intestinal perforation. At the initial clinical visit, the common causes of those abscesses, including spinal tuberculosis and urinary tract infection, were excluded. The treatment of the abscess was through an incision and drainage. However, the source of the abscess was not made clear, which led to an abscess recurrence and a delayed diagnosis of colorectal mucinous adenocarcinoma. After the patients were referred to our hospital, a definitive diagnosis of ascending colon mucinous adenocarcinoma was made with the help of tumor markers and colonoscopic findings. Because of the delayed diagnosis of the disease, two patients (case 1 and case 2) missed the chance of surgery due to disease progression and died in a short follow-up period. Only case 3 underwent radical surgery for the tumor in the right colon and partial abdominal wall resection and achieved a better prognosis. CONCLUSION: Abscesses in the right area of the lumbar spine, right groin, or right lower quadrant caused by non-intestinal perforation as the primary clinical manifestation of ascending colon mucinous adenocarcinoma are extremely rare. Mucinous adenocarcinoma of the ascending colon may be one of the causes of such abscesses. Performing colonoscopy as soon as possible is of great significance in the diagnosis and treatment of the disease.

MicroRNA­8063 targets heterogeneous nuclear ribonucleoprotein AB to inhibit the self­renewal of colorectal cancer stem cells via the Wnt/ß­catenin pathway.

The presence of cancer stem cells (CSCs) is a major cause of therapeutic failure in a variety of cancer types, including colorectal cancer (CRC). However, the underlying mechanisms that regulate the self­renewal of colorectal cancer stem cells (CRCSCs) remain unclear. Our previous study utilized CRCSCs and their parent cells; through gene microarray screening and bioinformatics analysis, we hypothesized that microRNA (miR)­8063 may bind to, and regulate the expression of, heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) to facilitate the regulation of CRCSC self­renewal. The aim of the present study was to confirm this conjecture through relevant experiments. The results indicated that compared with that in parent cells, miR­8063 expression was significantly downregulated in CRCSCs, while hnRNPAB expression was increased. Furthermore, hnRNPAB was identified as a direct target of miR­8063 using a dual­Luciferase assay. Overexpression of hnRNPAB promoted the acquisition of CSC characteristics in CRC cells (increased colony formation ability, enhanced tumorigenicity, and upregulated expression of CSC markers), as well as the upregulation of key proteins (Wnt3a, Wnt5a and ß­catenin) in the Wnt/ß­catenin signaling pathway. Similarly, after silencing miR­8063 in CRC cells, the characteristics of CSC were altered, and the expression of hnRNPAB protein was promoted. However, post overexpression of miR­8063 in CRCSCs, the self­renewal ability of CSCs was weakened with the downregulation of hnRNPAB protein, Wnt3a, Wnt5a and ß­catenin. These results suggest that as a tumor suppressor, miR­8063 is involved in regulating the self­renewal of CRCSCs, where loss of miR­8063 expression weakens its inhibition on hnRNPAB, which leads to the activation of Wnt/ß­catenin signaling to promote the self­renewal of CRCSCs.

One Approach Anterior Decompression and Fixation with Posterior Unilateral Pedicle Screw Fixation for Thoracolumbar Osteoporotic Vertebral Compression Fractures.

OBJECTIVE: The objective of the present paper was to explore the clinical effect of one approach anterior decompression and fixation with posterior unilateral pedicle screw fixation for thoracolumbar osteoporosis vertebral compression fractures (OVCF). METHODS: This is a single-center retrospective analysis. A total of six thoracolumbar OVCF patients (four women and two men) with an average age of 65.2 years (58-72 years) who were treated between June 2016 and May 2018 were enrolled in the present study. The lesion segments included: 1 case at T11, 1 case at T12, 3 cases at L1, and 1 case at L2. The six thoracolumbar OVCF patients were treated with one approach anterior decompression and fixation with posterior unilateral pedicle screw fixation. After general anesthesia, patients were placed in the right lateral decubitus position, an approximately 10-15-cm oblique incision was made along corresponding ribs, and the conventional left retroperitoneal and/or the extrapleural approach was performed for anterior lateral exposure. First, anterior decompression and fixation were performed, and then through the unilateral paraspinal muscle approach, posterior pedicle screw fixation was performed under the same incision. The back pain visual analogue scale (VAS), the Oswestry disability index (ODI), and the MacNab criteria were used to evaluate the clinical outcome. The radiographic analysis included the regional kyphosis angle and the fusion rate. Neurological status, operation time, intraoperative bleeding, the time of ambulation, hospital stay, and surgical complications were also assessed. RESULTS: Surgery was successful in all six patients, who were followed up for 31.6 months (range, 23-46 months). The operation time was 125-163 min, with a median of 135 min. The preoperative blood loss was 580-1230 mL, with a median of 760 mL. The time of ambulation was 3-5 days, with a median of 4.2 days. The hospital stay was 8-15 days, with the median of 10.5 days. According to the Frankel classification of neurological deficits, of two patients with grade C preoperatively, one had improved to grade D and one had improved to grade E at final follow up; among four patients with grade D preoperatively, at the final follow up one remained the same and three had improved to grade E. The postoperative back pain VAS score decreased significantly, from 6.17 ± 0.75 preoperatively to 0.83 ± 0.41 postoperatively (P < 0.05). The mean ODI score was 73.7 ± 5.86 preoperatively and reduced to 21.85 ± 3.27 postoperatively (P < 0.05). According to the MacNab criteria, at the final follow up, two patients rated their satisfaction as excellent, three patients as good, and one patient as fair. The mean regional kyphosis angle was 22.17° ± 6.01°before surgery, which improved to 9.33° ± 3.88° at the final follow up (P < 0.05). At the final follow up, there were two patients who had achieved a grade 2 bony fusion (33.3%), three patients grade 3 (50.0%), and one patient grade 4 (16.7%). No incision infections, internal fixation failures or other complications were found during the perioperative and the follow-up period. CONCLUSION: One approach anterior decompression and fixation with posterior unilateral pedicle screw fixation provides a novel method for thoracolumbar OVCF disease, with a satisfactory clinical outcome.