Skeletal muscle involvement in systemic amyloidosis is often overlooked.

AIM: Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated. METHODS: We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry. RESULTS: Twenty-eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light-chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL-λ, one with AL-κ and two with ATTR. Group 2 included 15 patients with AL-λ and two patients with AL-κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies. CONCLUSIONS: Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis.

Joint association of cardiovascular health and frailty with all-cause and cause-specific mortality: a prospective study.

BACKGROUND: Poor cardiovascular health (CVH) and physical frailty were reported to increase mortality risk, but their joint effects have not been fully elucidated. OBJECTIVES: We aimed to explore the separate and joint effects of CVH and frailty on mortality based on two perspectives of Life's Essential 8 (LE8) and Framingham Risk Score (FRS). METHODS: 21 062 participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were involved in this study. CVH was evaluated by the LE8 and FRS, and categorized into low, moderate and high CVH groups. Cox proportional hazard models were applied to estimate the separate and joint associations of CVH and frailty index (FI) with all-cause, cardiovascular disease (CVD) and cancer mortality. RESULTS: Over a median follow-up period of 87 months (95% CI: 86.0-88.0), 2036 deaths occurred. The separate linear dose-response relationships between CVH, frailty and mortality were observed (nonlinear P > .05). The combination of low CVH/frailty was negatively associated with all-cause mortality [hazard ratio (HR) and 95%CI: low LE8*FI, 5.30 (3.74, 7.52); high FRS*FI, 4.34 (3.20, 5.88)], CVD mortality [low LE8*FI, 6.57 (3.54, 12.22); high FRS*FI, 7.29 (3.92, 13.55)] and cancer mortality [low LE8*FI, 1.99 (1.14, 3.25); high FRS*FI, 2.32 (1.30, 4.15)], with high CVH/fit group as reference. Further stratified analyses showed that the combined burden of mortality from frailty and low CVH was greater among the young and females. CONCLUSIONS: Low CVH and frailty were independently and jointly correlated with greater risk of all-cause, CVD and cancer deaths, especially among the young and females.

Reproductive factors and cardiovascular health in post-menopausal women: a special focus on natural menopause.

Female-specific reproductive factors might contribute to increased risk of cardiovascular disease, and the American Heart Association (AHA) recently proposed Life's Essential 8 (LE8) score to quantify cardiovascular health (CVH). The study aimed to examine the relationships between reproductive factors and the LE8 score among post-menopause women in the United States. We enrolled 3223 post-menopause women from National Health and Nutrition Examination Survey (NHANES). CVH groups based on LE8 score were low (0-49), moderate (50-79), and high good CVH levels (80-100). Multivariate ordinal logistic regressions were applied to estimate the associations between reproductive factors and the LE8 score. In multivariate model, early menarche (OR: 0.69, 95 percent CI: 0.51-0.93) and early menopause (OR: 0.57, 95 percent CI: 0.43-0.77) were associated with LE8 score compared with normal menarche and menopause; Meanwhile, ages at menarche and menopause were positively correlated with LE8 score. The number of pregnancies and full-term pregnancies were negatively associated with LE8 (OR for per pregnancy increase and 95 percent CI, 0.93 (0.88, 0.98), 0.93 (0.87, 0.99), separately). Overall, natural menopausal women with early age at menarche and menopause, and a higher number of pregnancies may have a high risk of lower CVH, and need to focus on their CVH.

KOH-promoted cascade C-Cl bond activation and amidation of trichloromethyl aromatic compounds with formamides in water.

A KOH-promoted cascade C-Cl bond activation and amidation of trichloromethyl aromatic compounds with formamides using water as a solvent has been developed. This methodology suggested an alternative synthetic approach for the synthesis of aryl amide compounds in the absence of catalysts, additives and organic solvents. In addition, the yields of gram-scale reactions are good and provide a basis for synthetic application.

Two 3D Ln(III)-MOFs Based on Phosphineoxide Ligand: Synthesis, Structure Luminescent and Photocatalytic Properties.

Two new 3D metal-organic frameworks (MOFs) ZZUT1 and ZZUT2 were prepared through the reaction of tris-(4-carboxylphenyl) phosphineoxide (H3TPO) ligand with nitrate of neodymium and praseodymium by solvothermal method. The structure, fluorescence and photocatalytic properties of ZZUT1 and ZZUT2 were studied. The crystalline structure of two 3D Ln(III)-MOFs both exhibit triclinic system and P-1 space group. The results of fluorescence analysis showed that two 3D Ln(III)-MOFs could selectively recognize acetone molecule through the fluorescence quenching mechanism. Meanwhile, ZZUT1 and ZZUT2 showed good adsorption and degradation ability on organic dye methylene blue (MB) in photocatalytic condition, and the degradation efficiency can reach to more than 90%.

Discussion on the benefits of different treatment strategies in elderly and non-elderly patients with appendix MiNEN: a retrospective study based on SEER database.

PURPOSE: To investigate the benefits of surgery alone and postoperative chemotherapy in elderly and non-elderly patients with appendiceal mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) and analyze the factors affecting the prognosis of patients with MiNEN of the appendix. METHODS: Based on the Surveillance, Epidemiology, and End Results database (SEER) of the National Cancer Institute of the USA, 389 patients with appendiceal MiNENs from 2000 to 2016 were collected. All patients were distributed in the elderly group (≥ 60 years old) and the non-elderly group (< 60 years old) according to their age. The prognosis of the two groups of patients who received simple surgery and postoperative chemotherapy was analyzed and compared. The two treatment methods of the two tranches were matched by propensity score matching method. The effect of different treatment ways on the prognosis of sick persons was compared. The survivorship curves were painted by the Kaplan Meier method, log rank test was used to analyze the subsistence discrepancy of each group, and COX proportional risk model was used to analyze the factors affecting the prognosis of patients with appendiceal MiNENs. RESULTS: No matter the overall survival rate (OS) or cancer-specific mortality (CSM) of the two treatment schemes, the prognosis of patients in the only surgery group was meaningfully higher than that in the postoperative chemotherapy group, with statistically significant difference in component comparison (χ2 = 16.496, χ2 = 16.860, P < 0.001). After propensity score matching of patients in each group, there was no striking discrepancy in the OS of patients in the only surgery group compared with those in the postoperative chemotherapy group, regardless of whether they were elderly patients or non-elderly patients (χ2 = 3.205, χ2 = 1.521, all P > 0.05), the CSM consequences are fitting in with the OS. The consequences of the multivariate COX regression model showed that age (≥ 60 years old), sex (female), high histological grade, and lymph node positive were all the influencing factors for the poor OS of patients with MiNEN; the CSM results are consistent with the OS. CONCLUSION: For patients with appendix MiNEN, whether elderly or non-elderly patients (especially for non-elderly patients), surgical treatment may be a better choice.

Balancing adipocyte production and lipid metabolism to treat obesity-induced diabetes with a novel proteoglycan from Ganoderma lucidum.

Obesity is often accompanied by metabolic disorder and insulin resistance, resulting in type 2 diabetes. Based on previous findings, FYGL, a natural hyperbranched proteoglycan extracted from the G. lucidum fruiting body, can decrease blood glucose and reduce body weight in diabetic mice. In this article, the underlying mechanism of FYGL in ameliorating obesity-induced diabetes was further investigated both in vivo and in vitro. FYGL upregulated expression of metabolic genes related to fatty acid biosynthesis, fatty acid ß-oxidation and thermogenesis; downregulated the expression of insulin resistance-related genes; and significantly increased the number of beige adipocytes in db/db mice. In addition, FYGL inhibited preadipocyte differentiation of 3T3-L1 cells by increasing the expression of FABP-4. FYGL not only promoted fatty acid synthesis but also more significantly promoted triglyceride degradation and metabolism by activating the AMPK signalling pathway, therefore preventing fat accumulation, balancing adipocyte production and lipid metabolism, and regulating metabolic disorders and unhealthy obesity. FYGL could be used as a promising pharmacological agent for the treatment of metabolic disorder-related obesity.

Bioengineered Enzymes and Precision Fermentation in the Food Industry.

Enzymes have been used in the food processing industry for many years. However, the use of native enzymes is not conducive to high activity, efficiency, range of substrates, and adaptability to harsh food processing conditions. The advent of enzyme engineering approaches such as rational design, directed evolution, and semi-rational design provided much-needed impetus for tailor-made enzymes with improved or novel catalytic properties. Production of designer enzymes became further refined with the emergence of synthetic biology and gene editing techniques and a plethora of other tools such as artificial intelligence, and computational and bioinformatics analyses which have paved the way for what is referred to as precision fermentation for the production of these designer enzymes more efficiently. With all the technologies available, the bottleneck is now in the scale-up production of these enzymes. There is generally a lack of accessibility thereof of large-scale capabilities and know-how. This review is aimed at highlighting these various enzyme-engineering strategies and the associated scale-up challenges, including safety concerns surrounding genetically modified microorganisms and the use of cell-free systems to circumvent this issue. The use of solid-state fermentation (SSF) is also addressed as a potentially low-cost production system, amenable to customization and employing inexpensive feedstocks as substrate.

Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug-induced liver injury: A multicenter, randomized, phase II trial.

BACKGROUND AND AIMS: Evidence for using bicyclol in drug-induced liver injury (DILI) is limited. This study aimed to explore the efficacy and safety of bicyclol in acute DILI. METHODS: This was a multicenter, randomized, double-blinded, double-dummy, active-controlled, superiority and phase II trial. Patients with idiosyncratic acute DILI were randomized 1: 1:1 to low-dose bicyclol (25 mg times a day [TID]), high-dose bicyclol (50 mg TID) and polyene phosphatidylcholine (control) groups. The primary endpoint was the decrease from baseline in serum alanine aminotransferase (ALT) levels at post-treatment for 4 weeks. RESULTS: Overall, 241 patients were included in the full analysis set, with 81, 82 and 78 patients in the low-dose bicyclol, high-dose bicyclol, and control groups respectively. ALT levels decreased across groups (-249.2 ± 151.1, -273.6 ± 203.1, and -180.8 ± 218.2 U/L in the low-dose bicyclol, high-dose bicyclol and control groups, respectively; both p < .001, the bicyclol-dependent groups vs. control group). The ALT normalization rates at weeks 1, 2, 4, 6 and 8 were higher in the bicyclol-dependent groups than in the control group (p = .002 at week 1 and all p < .001 at weeks 2, 4, 6 and 8 respectively). The median times to ALT normalization in the low-dose bicyclol, high-dose bicyclol and control groups were 29, 16 and 43 days respectively. Adverse events, serious adverse events and adverse drug reactions were similar across groups. CONCLUSIONS: Bicyclol (25 and 50 mg TID) appeared efficacious and safe for treating idiosyncratic acute DILI, while bicyclol 50 mg TID showed higher efficacy. TRIAL REGISTRATION NUMBER: www. CLINICALTRIALS: gov (registration no. NCT02944552).

Thioamide directed iridium(I)-catalyzed C-H arylation of ferrocenes with aryl boronic acids.

The first Ir(I)-catalyzed thioamide-assisted C-H arylation of ferrocenes with aryl boronic acids under base-free mild reaction conditions in the presence of Ag2CO3 as an oxidant with eco-friendly 2-MeTHF as a solvent was developed. This reaction has a wide range of substrates (37 examples) and functional group tolerance (18-94% yields), and provides promising access to aryl thioamide-ferrocene compounds with good yields and regioselectivity.

Development and psychometric evaluation of a lymphoedema self-management behaviour questionnaire for breast cancer patients.

OBJECTIVES: The study was aimed to develop and evaluate a lymphoedema self-management behaviour questionnaire (LSMBQ) for breast cancer patients. METHODS: The initial version of the behaviour questionnaire was developed based on the framework of self-management and the evidence summary of lymphoedema self-management. Two rounds of expert consultation were conducted to validate the questionnaire's content validity. A cross-sectional survey was then conducted in breast wards of two hospitals in China to evaluate the reliability and validity of this scale. Exploratory structural equation model was used to test the construct validity. T-test was used to analyse the known group validity. Structural equation model was applied to verify the relationship between self-efficacy, social support, and lymphoedema self-management behaviour to test the convergent validity. Also, the internal consistency reliability and test-retest reliability were evaluated. RESULTS: The questionnaire's content validity was satisfactory. There were 22 items included in the LSMBQ for validation and 260 completed the survey. A six-factor structure with good construct validity was identified. The result of t-test verified that patients who knew the risk of lymphoedema and those who received lymphoedema health education had higher scores of lymphoedema self-management behaviours (P < 0.05), indicating that the questionnaire has good known group validity. The fitting results of the structural equation model indicated that the 22-item questionnaire had good convergent validity. Cronbach's alpha coefficients and test-retest reliability for the total questionnaire were 0.910 and 0.875, respectively. CONCLUSIONS: The 22-item LSMBQ appears to have adequate reliability and validity to assess the lymphoedema self-management behaviours for breast cancer patients.

Ecological thresholds of toxic plants for sheep production and ecosystem multifunctionality and their trade-off in an alpine meadow.

Toxic plants are a natural component of alpine meadow which co-evolved with Tibetan sheep for thousands of years. One challenge for indigenous herders is to know the ecological thresholds of toxic plants and maintain their vital functions in ways that are compatible with economic income and ecological conservation. To achieve this, field trials with Tibetan sheep grazing in alpine meadow were conducted to examine the ecological thresholds of toxic plants for sheep production and ecosystem functions and their trade-offs. Our results demonstrated that the changing point values of biomass proportion of toxic plants for dry matter intake and liveweight gain of sheep were 17% and 22%, respectively. The changing point value of biomass (richness) proportion of toxic plants for soil carbon accumulation index was 31% (59%), for soil nutrient cycling index was 38% (42%), and for ecosystem multifunctionality index was 28% (50%). The trade-off between liveweight gain of sheep and ecosystem multifunctionality first decreased and then increased along the gradient of biomass proportion of toxic plants (the value of changing point was 37%), and had a significant negative correlation with richness of toxic plants. In addition, structural equation modeling indicated that toxic plants can affect the trade-off between liveweight gain of sheep and ecosystem multifunctionality though increasing acid detergent fiber of plant and decreasing plant species richness, belowground biomass and soil total phosphorus. Consequently, opinions towards toxic plants should shift from the conventional view that they are serious threat to grassland ecosystem health to an inclusive understanding that they are beneficial to livestock and ecosystem functions under certain ecological thresholds.

Microencapsulation of Flaxseed Oil by Lentil Protein Isolate-κ-Carrageenan and -ι-Carrageenan Based Wall Materials through Spray and Freeze Drying.

Lentil protein isolate (LPI)-κ-carrageenan (κ-C) and -ι-carrageenan (ι-C) based microcapsules were prepared through spray-drying and freeze-drying to encapsulate flaxseed oil in order to reach final oil levels of 20% and 30%. Characteristics of the corresponding emulsions and their dried microcapsules were determined. For emulsion properties, all LPI-κ-C and LPI-ι-C emulsions remained 100% stable after 48 h, while the LPI emulsions destabilized quickly (p < 0.05) after homogenization mainly due to low emulsion viscosity. For spray-dried microcapsules, the highest yield was attributed to LPI-ι-C with 20% oil, followed by LPI-κ-C 20% and LPI-ι-C 30% (p < 0.05). Flaxseed oil was oxidized more significantly among the spray-dried capsules compared to untreated oil (p < 0.05) due to the effect of heat. Flaxseed oil was more stable in all the freeze-dried capsules and showed significantly lower oil oxidation than the untreated oil after 8 weeks of storage (p < 0.05). As for in vitro oil release profile, a higher amount of oil was released for LPI-κ-C powders under simulated gastric fluid (SGF), while more oil was released for LPI-ι-C powders under simulated gastric fluid and simulated intestinal fluid (SGF + SIF) regardless of drying method and oil content. This study enhanced the emulsion stability by applying carrageenan to LPI and showed the potential to make plant-based microcapsules to deliver omega-3 oils.

Passive polarimetric imaging of millimeter and terahertz waves for personnel security screening.

Passive millimeter and terahertz wave imaging is a powerful way for personnel security inspection and scene monitoring. The existing systems usually have a single polarization mode. To obtain more information, polarimetric imaging has been preliminarily explored recently. However, there is no work exhibiting high-performance polarimetric imaging to analyze and interpret polarization characteristics. In this Letter, we report on the development of a W-band passive polarimetric imaging system for human body screening and present the polarization characteristics analysis of several typical scenarios. The experimental system has a spatial resolution of better than 2 cm at 2.5 m distance and has a thermal sensitivity of better than 0.3 K. The system can display polarization properties of human bodies and concealed objects. The experimental results demonstrate that passive polarimetric imaging has a great potential for object contrast enhancement, detection, segmentation, and recognition.

Circ_PGPEP1 Serves as a Sponge of miR-1297 to Promote Gastric Cancer Progression via Regulating E2F3.

BACKGROUND: Circular RNA (circRNA) is a special kind of noncoding RNA that plays a vital function in the progression of gastric cancer (GC). However, the role of a new circRNA, circ_PGPEP1, in GC is unclear. AIMS: Exploring the role and mechanism of circ_PGPEP1 in GC progression. METHODS: The expression levels of circ_PGPEP1, miR-1297, and E2F transcription factor 3 (E2F3) were determined using quantitative real-time PCR. Flow cytometry, colony formation assay, MTT assay, and transwell assay were used to evaluate cell cycle, apoptosis, proliferation, migration, and invasion. The protein levels of apoptosis-related markers and E2F3 were measured by western blot analysis. The interaction between circ_PGPEP1 and miR-1297 or miR-1297 and E2F3 was confirmed by dual-luciferase reporter assay. In addition, animal experiments were performed to assess the effect of circ_PGPEP1 on GC tumor growth in vivo. RESULTS: Circ_PGPEP1 was a highly expressed circRNA in GC. Loss-of-function experiment indicated that circ_PGPEP1 silencing could induce cell cycle arrest and apoptosis, while inhibit proliferation, migration, and invasion in GC cells. MiR-1297 could be sponged by circ_PGPEP1, and its expression was downregulated in GC. MiR-1297 inhibitor could reverse the negatively regulation of circ_PGPEP1 knockdown on GC progression. Furthermore, we also found that E2F3 could be targeted by miR-1297, and its expression was positively regulated by circ_PGPEP1. Overexpression of E2F3 could invert the inhibitory effect of miR-1297 on GC progression. Animal experiments suggested that silenced circ_PGPEP1 could reduce GC tumor growth. CONCLUSION: Our research showed that circ_PGPEP1 might serve as a potential biomarker for GC.

A novel prognosis prediction model, including cytotoxic T lymphocyte-associated antigen-4, ischemia-modified albumin, lipoprotein-associated phospholipase A2, glial fibrillary acidic protein, and homocysteine, for ischemic stroke in the Chinese hypertensive population.

BACKGROUND: There is still a lack of tools to assess the prognosis of ischemic stroke patients induced by hypertension. In this study, we built a novel prognostic assessment model for ischemic stroke in the Chinese hypertensive population. METHODS: Mass spectrometry technique was used to analyze the changes in serum protein profiles of hypertensive patients with ischemic stroke. A total of 314 hypertensive patients were divided into the testing group (206 patients) and the validation group (108 patients). RESULTS: Compared with hypertensive patients without ischemic stroke, serum cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), ischemia-modified albumin (IMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), glial fibrillary acidic protein (GFAP), and homocysteine (HCY) levels were significantly increased among hypertensive patients with ischemic stroke (p < 0.05). Then, we built a novel prognostic assessment model for hypertensive patients with ischemic stroke [Logit(P) = 29.172-1.088*CTLA-4-0.952*IMA-0.537*Lp-PLA2 -0.066*GFAP -0.149*HCY]. It showed higher efficiency (AUC = 0.981, sensitivity = 95.5%, specificity = 93.8%) than any single marker. The estimated probability was 0.739, which means if higher than 0.739, it was classified into poor prognosis. Compared with the estimated probability ≤0.739 group, the survival rate of hypertensive patients with ischemic stroke in the estimated probability >0.739 group was significantly decreased (χ2  = 40.001, p < 0.001). In the validation group, our novel prognostic assessment model still showed good efficiency (AUC = 0.969, sensitivity = 89.4%, specificity = 92.5%; χ2  = 47.551, p < 0.001). CONCLUSION: Current novel prognostic assessment model we have built is of great value in the prognostic evaluation for ischemic stroke in the Chinese hypertensive population.

Concealed object enhancement using multi-polarization information for passive millimeter and terahertz wave security screening.

Passive millimeter and terahertz wave imaging has become a significant potential technique for human security check and scene monitoring. Due to the small difference of the brightness temperatures between human body and concealed objects, the temperature sensitivity and spatial resolution of radiometers are always the key performance indexes which are difficult to improve. Therefore, when the hardware performance is given, improving detectivity becomes a pressing need. In this paper, a physically-based concealed object enhancement method using multi-polarization information is presented. The polarization model and polarization property of human body and concealed objects have been analyzed. By fusing multiple polarization images, we can obtain a complete polarization image in which the contrast between human body and concealed objects is enhanced and stable. The experimental results of simulation and measurement demonstrate the enhancement performance, and Differential Signal Noise Ratio (DSNR) is obviously improved by using the proposed method.

A target-mediated fuel-initiated molecular machine for high-sensitive fluorescence assay of the ZIKV gene via strand displacement reaction-based signal recovery and cycling amplification.

Zika virus (ZIKV) is a serious threat to human health due to its widespread human arboviral infections, and early diagnosis is one of the keys to preventing infections from spreading, but there is a lack of highly sensitive and specific detection. In this work, a target-mediated fuel-initiated molecular machine was proposed for the high-sensitive fluorescence assay of the ZIKV gene via strand displacement reaction-based signal recovery and cycling amplification. The molecular machine was prepared by modifying AuNP surfaces with specially designed lock-like DNAs (LLDs). The LLDs assembled with a hairpin DNA (H1) and a fluorescent aDNA can be opened under the trigger of the ZIKV gene and the strand displacement reactions are further initiated with the help of the DNA fuel (H2), which results in the release of the aDNAs and ZIKV genes from the AuNPs, causing the recovery of the fluorescence signal and the cyclic amplification of the gene. The target-mediated fuel-initiated molecular machines output an amplified fluorescence signal with the enhancement of 360%, and possess good sensitivity for detecting the ZIKV gene in serum with a linear calibration curve from 100 pM to 1 fM and a low limit of detection of 0.90 fM. The molecular machines can differentiate the ZIKV gene from the single base mismatched DNA obviously and show good recovery of ZIKV gene detection, which demonstrates the good specificity, reproducibility and reliability of the highly sensitive assay for the early detection of the virus.

Lnc-MAP6-1:3 knockdown inhibits osteosarcoma progression by modulating Bax/Bcl-2 and Wnt/ß-catenin pathways.

Osteosarcoma (OS) is the most common type of malignant bone tumor that affects children and adolescents. Still, the cellular and molecular mechanisms driving the development of this disease remain poorly understood. In this study, numerous dysregulated lncRNAs were identified by RNA-seq. As a result, we were able to find a novel lncRNA Lnc-MAP6-1:3 which is highly expressed in osteosarcoma. Using a set of approaches including gene knockdown, RT-PCR, oncogenic function assay and western blotting, we observed that knockdown of Lnc-MAP6-1:3 expression suppressed cell proliferation and colony formation, and promoted apoptosis in vitro. For the first time, we have identified that Lnc-MAP6-1:3 potentially influence the malignant behavior of osteosarcoma via Bax/Bcl-2 and Wnt/ß-catenin signaling pathways. Henceforth, Lnc-MAP6-1:3 may provide a new molecular route of research and therapeutic applications for the diagnosis and treatment of osteosarcoma.

Sphingosine-1-phosphate alleviates irradiation-induced parotid injury in a miniature pig model.

OBJECTIVES: Our aim was to verify the alleviation effect of sphingosine-1-phosphate (S1P) in a miniature pig model. MATERIAL AND METHODS: Thirty male miniature pigs were randomly separated into 10 groups in our experiment. We administered S1P through the parotid duct in a retrograde fashion 2 hr before irradiation (IR). The salivary flow rate and blood flow rate were tested 20 weeks after IR. The apoptotic level was checked at 12, 24 hr and 7 days post-IR. RESULTS: Twenty weeks after IR, the salivary flow rate of the IR-side parotid gland in IR + S1P group can be maintained at about 40% of the non-IR side, while only 20% was maintained in the IR group. The blood flow rate and microvascular density were significantly higher in the IR + S1P group than in the IR group. The apoptotic level and cleaved caspase-3 expression were downregulated in IR + S1P group, and the ratio of Bcl-2/Bax was increased. The blood flow rate and CD31 level were significantly restored at 12, 24 hr and 7 days post-IR. CONCLUSION: Sphingosine-1-phosphate may partially alleviate IR-induced parotid dysfunction by decreasing apoptosis of microvascular endothelial cells and maintaining the blood flow rate.