Long noncoding RNA LINC00675 drives malignancy in acute myeloid leukemia via the miR-6809 -CDK6 axis.

Hematological malignancies such as acute myeloid leukemia (AML) have a low cure rate and a high recurrence rate. Long noncoding RNAs (LNCs) are essential regulators of tumorigenesis and progression. The role of lncRNA LINC00675 in AML has rarely been reported. This study revealed elevated LINC00675 expression in AML that promotes proliferation and inhibits apoptosis. Mechanistically, LINC00675 combines with miR-6809 to promote the expression of CDK6 in vitro and in vivo. Immune-checkpoint genes were expressed more highly in LINC00675-high patients. A high level of LINC00675 expression may make patients more susceptible to palbociclib treatments. In conclusion, our study demonstrated that LINC00675 is an oncogenic lncRNA that enhances the malignancy of AML by upregulating CDK6 expression through miR-6809 sponging, providing a new perspective and feasible target for the diagnosis and treatment of AML.

The effect of overweight or obesity on osteoporosis: A systematic review and meta-analysis.

BACKGROUND: Osteoporosis and obesity are closely related, and the relationships between different types of obesity and osteoporosis are inconsistent. OBJECTIVE: Our objective was to summarize earlier data concerning the association between osteoporosis and obesity (general and central), and to compare the impacts of these two obesity indicators on osteoporosis. METHODS: From inception to May 2021, a comprehensive search in electronic bibliographic databases was conducted, and the search was updated in December 2021, July 2022 and June 2023. The data were independently extracted and evaluated by two investigators from epidemiological studies that reported the impact of obesity on the odds of incident osteoporosis. RESULTS: There were 24 studies included in the final analysis when it came to general obesity measured by body mass index (BMI). Individuals with overweight and obesity had decreased odds of osteoporosis (odds ratio (OR), 0.451, 95% confidence intervals (CIs): 0.366-0.557). Sensitivity analyses showed that both overweight and obesity were decreased odds of osteoporosis, with reductions of 48.6% and 70.1%, respectively (OR, 0.514, 95% CI: 0.407-0.649; OR, 0.299, 95% CI: 0.207-0.433). Conversely, individuals classified as underweight were found to have higher odds of osteoporosis (OR, 2.540, 95% CI: 1.483-4.350). In term of central obesity, the final analysis consisted of 7 studies. No significant association was observed between central obesity and osteoporosis (OR, 0.913, 95% CI: 0.761-1.096). CONCLUSIONS: General overweight and obesity were associated with lower odds of developing osteoporosis, whereas underweight was associated with higher odds. However, central obesity did not show a significant association with osteoporosis. These findings underscore the importance of considering the impact of obesity on osteoporosis. Further research is necessary to reinforce the evidence and validate our findings.

The Weight-loss Effect of GLP-1RAs Glucagon-Like Peptide-1 Receptor Agonists in Non-diabetic Individuals with Overweight or Obesity: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity. OBJECTIVE: To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes. METHODS: This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models. RESULTS: Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m2, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects. CONCLUSIONS: The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.

The effect of calcium supplementation in people under 35 years old: A systematic review and meta-analysis of randomized controlled trials.

Background: The effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years). Methods: This is a systematic review and meta-analysis. The Pubmed, Embase, ProQuest, CENTRAL, WHO Global Index Medicus, Clinical Trials.gov, WHO ICTRP, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases were systematically searched from database inception to April 25, 2021. Randomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old. Results: This systematic review and meta-analysis identified 43 studies involving 7,382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (standardized mean difference [SMD] 0.627, 95% confidence interval [CI] 0.338-0.915; SMD 0.364, 95% CI 0.134-0.595; respectively) and total body (SMD 0.330, 95% CI 0.163-0.496; SMD 0.149, 95% CI 0.006-0.291), also with a slight improvement effect on lumbar spine BMC (SMD 0.163, 95% CI 0.008-0.317), no effects on total hip BMD and BMC and lumbar spine BMD were observed. Very interestingly, subgroup analyses suggested that the improvement of bone at femoral neck was more pronounced in the peripeak bone mass (PBM) population (20-35 years) than the pre-PBM population (<20 years). Conclusions: Our findings provided novel insights and evidence in calcium supplementation, which showed that calcium supplementation significantly improves bone mass, implying that preventive calcium supplementation before or around achieving PBM may be a shift in the window of intervention for osteoporosis. Funding: This work was supported by Wenzhou Medical University grant [89219029].

Osteoporosis and bone fractures are common problems among older people, particularly older women. These conditions cause disability and reduce quality of life. Progressive loss of bone mineral density is usually the culprit. So far, strategies to prevent bone weakening with age have produced disappointing results. For example, taking calcium supplements in later life only slightly reduces the risk of osteoporosis or fracture. New approaches are needed. Bone mass increases gradually early in life and peaks and plateaus around 20-35 years of age. After that period, bone mass slowly declines. Some scientists suspect that increasing calcium intake during this period of peak bone mass may reduce osteoporosis or fracture risk later in life. A meta-analysis by Liu, Le et al. shows that boosting calcium intake in young adulthood strengthens bones. The researchers analyzed data from 43 randomized controlled trials that enrolled 7,382 participants. About half the studies looked at the effects of taking calcium supplements and the other half analyzed the effects of a high calcium diet. Boosting calcium intake in people younger than age 35 improved bone mineral density throughout the body. It also increased bone mineral density at the femoral neck, where most hip fractures occur. Calcium supplementation produced larger effects in individuals between the ages of 20 and 35 than in people younger than 20. Both high calcium diets and calcium supplements with doses less than 1000 mg/d boosted bone strength. Higher dose calcium supplements did not provide any extra benefits. The analysis suggests people should pay more attention to bone health during early adulthood. Large randomized clinical trials are needed to confirm the long-term benefits of boosting calcium intake during early adulthood. But if the results are validated, taking calcium supplements, or eating more calcium-rich foods between the ages of 20 and 35 may help individuals build healthier bones and prevent fractures and osteoporosis later in life.

Effect of high-protein vs. high-fat snacks before lunch on glycemic variability in prediabetes: A study protocol for a randomized controlled trial.

Background: China has the largest number of patients with Type 2 Diabetes Mellitus (T2DM), and it tends to increasingly grow in the future, putting an enormous burden on disease control and prevention in China. While glycemic variability (GV) came to be an important indicator of blood glucose control in diabetic patients, studies suggested that premeal snacks may help blood glucose control, but there are still some problems to be researched. Therefore, we designed this trial to evaluate which kind of premeal snacks would lead to better effects on GV under two diet patterns in pre-diabetes subjects and to evaluate assessments of acceptability and compliance, behavior, and metabolism changes in individuals will be described. Methods and analysis: The study is a single-center, open-label, multiparallel group, randomized controlled trial. A total of 32 male and female volunteers will be randomized into 4 groups in a single allocated ratio of soy milk (powder) snack, milk (powder) snack, almonds snack, and placebo control with 250 ml of water taken 30 min before lunch, respectively. The study consists of two intervention periods over 11 days. The first intervention period under habitual diet conditions from D3 to D6 (4 days), during which all subjects are asked to maintain their habitual eating and daily activities similar to the run-in period. The second intervention consists of prelunch snacks with standard meals. We will examine both the effect of GV and various metabolic and behavioral outcomes potentially associated with the interventions. At the end of this study, we will assess the acceptability and maintainability of the intervention through interviews. Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2200058935.

LSTNet: A Reference-Based Learning Spectral Transformer Network for Spectral Super-Resolution.

Hyperspectral images (HSIs) are data cubes containing rich spectral information, making them beneficial to many Earth observation missions. However, due to the limitations of the associated imaging systems and their sensors, such as the swath width and revisit period, hyperspectral imagery over a large coverage area cannot be acquired in a short amount of time. Spectral super-resolution (SSR) is a method that involves learning the relationship between a multispectral image (MSI) and an HSI, based on the overlap region, followed by reconstruction of the HSI by making full use of the large swath width of the MSI, thereby improving its coverage. Much research has been conducted recently to address this issue, but most existing methods mainly learn the prior spectral information from training data, lacking constraints on the resulting spectral fidelity. To address this problem, a novel learning spectral transformer network (LSTNet) is proposed in this paper, utilizing a reference-based learning strategy to transfer the spectral structure knowledge of a reference HSI to create a reasonable reconstruction spectrum. More specifically, a spectral transformer module (STM) and a spectral reconstruction module (SRM) are designed, in order to exploit the prior and reference spectral information. Experimental results demonstrate that the proposed method has the ability to produce high-fidelity reconstructed spectra.

Relationship between Hepatitis B virus infection and platelet production and dysfunction.

Hepatitis B virus (HBV) is a kind of hepatotropic DNA virus. The main target organ is liver, except for liver, HBV has been found in a variety of extrahepatic tissues, such as kidney, thyroid, pancreas, bone marrow, etc. HBV can cause severe complications by invading these tissues. Among them, pancytopenia is one of the common complications, especially thrombocytopenia that causes life-threatening bleeding. However, the mechanism of thrombocytopenia is unclear and the treatment is extremely difficult. It has been confirmed that HBV has a close relationship with platelets. HBV can directly infect bone marrow, inhibit platelet production, and accelerate platelet destruction by activating monocyte-macrophage system and immune system. While platelets act as a double-edged sword to HBV. On one hand, the activated platelets can degranulate and release inflammatory mediators to help clear the viruses. Furthermore, platelets can provide anti-fibrotic molecules to improve liver functions and reduce hepatic fibrosis. On the other hand, platelets can also cause negative effects. The infected platelets collect HBV-specific CD8+ T cells and nonspecific inflammatory cells into liver parenchyma, inducing chronic inflammation, liver fibrosis and hepatic carcinoma. This article explores the interaction between HBV infection and platelets, providing a theoretical basis for clinical treatment of thrombocytopenia and severe hemorrhage caused by HBV infection.

Regression Analysis and Comparison of Economic Parameters with Different Light Index Models under Various Constraints.

Economic globalization is developing more rapidly than ever before. At the same time, economic growth is accompanied by energy consumption and carbon emissions, so it is particularly important to estimate, analyze and evaluate the economy accurately. We compared different nighttime light (NTL) index models with various constraint conditions and analyzed their relationships with economic parameters by linear correlation. In this study, three indices were selected, including original NTL, improved impervious surface index (IISI) and vegetation highlights nighttime-light index (VHNI). In the meantime, all indices were built in a linear regression relationship with gross domestic product (GDP), employed population and power consumption in southeast China. In addition, the correlation coefficient R2 was used to represent fitting degree. Overall, comparing the regression relationships with GDP of the three indices, VHNI performed best with the value of R2 at 0.8632. For the employed population and power consumption regression with these three indices, the maximum R2 of VHNI are 0.8647 and 0.7824 respectively, which are also the best performances in the three indices. For each individual province, the VHNI perform better than NTL and IISI in GDP regression, too. When taking employment population as the regression object, VHNI performs best in Zhejiang and Anhui provinces, but not all provinces. Finally, for power consumption regression, the value of VHNI R2 is better than NTL and IISI in every province except Hainan. The results show that, among the indices under different constraint conditions, the linear relationships between VHNI and GDP and power consumption are the strongest under vegetation constraint in southeast China. Therefore, VHNI index can be used for fitting analysis and prediction of economy and power consumption in the future.

Expression and Relationship of SAMHD1 with Other Apoptotic and Autophagic Genes in Acute Myeloid Leukemia Patients.

BACKGROUND: SAM domain- and HD domain-containing protein 1 (SAMHD1) is a cellular enzyme which is responsible for blocking replication in viruses and participates in the progression of many cancers. OBJECTIVE: The aim of this study was to correlate the expression level of SAMHD1 with other apoptotic and autophagic genes in acute myeloid leukemia (AML) patients. METHODS: In the present study, mRNA levels of SAMHD1 with other apoptotic and autophagic-related genes were evaluated in patients who were newly diagnosed with AML. RESULTS: SAMHD1, Bcl-xl, Bax, Bak, XIAP, and cIAP1 were downregulated in the AML group compared to the non-AML group (p < 0.05). SAMHD1 expression did not correlate with the other genes, while most apoptotic genes were positively correlated with each other. SAMHD1 expression was not associated with the blood routine or blast percentage of the AML patients, while Bax, Bak, cIAP2, and LC3 were significantly correlated with white blood cells. No statistically significant differences were found between the studied genes and prognosis stratifications, but Bcl-xl, Bak, cIAP1, and Mcl-1, LC3 were expressed at lower levels in the unfavorable AML group compared to the controls. CONCLUSION: SAMHD1 and Bcl-xl, Bax, Bak, XIAP, and cIAP1 were downregulated in AML patients, while there were no significant differences in the clinical characteristics and prognosis with reference to SAMHD1 expression.

NAT10 upregulation indicates a poor prognosis in acute myeloid leukemia.

BACKGROUND: N-acetyltransferase 10 (NAT10) is considered as an oncogene in many tumors. This study investigated the NAT10 expression in Chinese acute myeloid leukemia (AML) patients and evaluated the predictive significance of NAT10 with a single-center retrospective study. METHODS: The Oncomine was used to analyze NAT10 expression in AML. We also collected bone marrow samples of 48 newly diagnosed AML patients and 20 benign individuals in our center. NAT10 mRNA expression levels were detected by real-time qPCR. Clinical data was obtained from inpatient medical records. RESULTS: Two microarrays in Oncomine showed that NAT10 was upregulated in AML. Our data revealed that AML patients had higher NAT10 expression levels than the normal controls (P < 0.01). NPM1-mutant patients had higher NAT10 mRNA levels than NPM1-wt patients. NAT10 expression level was higher in nonremission group than in overall remission group (P < 0.05). High NAT10 expression indicated a poor progression-free survival and overall survival. CONCLUSIONS: The results support NAT10 as a potential prognostic and therapeutic biomarker for AML.

Investigation of candidate molecular biomarkers for expression profile analysis of the Gene expression omnibus (GEO) in acute lymphocytic leukemia (ALL).

Much progress has been made in understanding the mechanism of acute lymphocytic leukemia (ALL). However, for adult ALL, there is still a lack of an effective treatment. In the present study, we first used the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between ALL cell lines and Hodgkin and non-Hodgkin cell lines. Then, the GEO database was also used to detect the DEGs in acute lymphoblastic leukemia (Reh) cells transfected with a normal control or a constitutively active variant of the IkB kinase ß. Finally, we found that three key DEGs (CCL5, FSCN1, and HS3ST1) are involved in proliferation and apoptosis according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) pathway analyses. Finally, we determined that all three target genes that participate in proliferation and apoptosis are regulated via the NF-kB signaling pathway.

[Embelin Reverses the Multi-drug Resistance of K562/D to Daunorubicin Independently of P-gp and MDR1 mRNA].

OBJECTIVE: To investigate the mechanism of reversing drug resistance of K562/D cells to daunorubicin by Embelin and its relationship with P-gp and MDR1 mRNA. METHODS: MTT assay was used to detect and compare the cell proliferation rate of treating with DNR alone and DNR combined with Embelin. Flow cytometry with Annexin V-FITC/PI double staining was used to detect cell apoptosis rate, Western blot was used to detect the expression of XIAP,Caspase-3,BCL-2,BAX and P-gp of K562/D cells after using DNR alone and combining with Embelin. Quantitative real-time PCR was used to detect XIAP,BCL-2,BAX and MDR1 mRNA. RESULTS: The IC50 of K562 and K562/D cells treated with DNR for 24 h were 2.177 µg/ml and 69.43 µg/ml, respectively. The drug-resistance index was 31.89; The proliferation inhibition rates of K562/D cells treated with Embelin of 3, 10, 30, 100 and 300 µg/ml for 24 h were 2.70%±1.08%, 10.92%±4.89%, 28.13%±2.09%, 36.56%±3.24% and 43.59%±1.16%; The proliferation inhibition rates of K562/D cells treated with DNR of 0.1, 1, 10 and 100 µg/ml combined with 10 µg/ml Embelin for 24 h were 31.92%±3.29%, 49.57%±6.87%, 55.16%±0.78% and 71.94%±3.89%. The IC50 was 2.11 µg/ml respectively. The reverse index was 32.91. The apoptosis rates of K562/D cells treated with 0.1 µg/ml DNR alone or combined with Embelin of 10 µg/ml and 30 µg/ml for 24 h were 12.06%±0.95%, 27.54%±0.59% and 39.59%±1.57%, respectively. The results of Western blot showed that after combination of DNR with Embelin, the expression of Caspase-3 was significantly down-regulated (P<0.05), moreover, the prolifiration inhibition effect of drug combination on cells could be countreacted by Z-VAD-FMK, at the same time the expression of XIAP and BCL-2 protein was significantly down-regulated(P<0.05), the expression of BAX protein was significantly up-regulated(P<0.05), while there was no change of P-gp expression later (P<0.05). The results of RT-PCR showed that after combination of DNR with Embelin, expression of XIAP and BCL-2 mRNA was significantly down-regulated(P<0.05), expression of BAX mRNA was significantly up-regulated(P<0.05), while there was no obvious change of MDR1 mRNA expression(P>0.05). CONCLUSION: The down-regulation of XIAP contributes to enhance the effect of DNR on K562/D cells, the mechanism of Embelin-reversing the drug-resistence of K562/D cells to DNR does not relate with P-gp and MDR1 mRNA.

[Latest advances of research on autophagy and leukemia treatment].

Autophagy, as a conservative self-degradative approach of eukaryotic cells, plays an important role in cellular growth, proliferation,differentiation, death and keeping intracellular steady state. On one hand, autophagy can protect tumor cells to keep survival; on the other hand, autophagy can lead to apoptosis of leukemia cells. The double-edged impacts of autophagy make it to be the hotspot for research on mechanism and treatment of leukemia. This article reviews the diverse effects of autophagy in different leukemia cell lines, as well as its corresponding mechanism resulting in drug resistance, so as to provide theoretic guide for direct rational application of drugs according to their various mechnisms.

The XIAP inhibitor Embelin enhances TRAIL-induced apoptosis in human leukemia cells by DR4 and DR5 upregulation.

The present study was designed to explore the effects of low-toxicity Embelin on TRAIL-induced apoptosis and its possible mechanism in human leukemia cells. Our study showed that low-toxicity Embelin enhanced TRAIL-induced apoptosis through DR4 and DR5 upregulation and caspase activation in HL-60 cells. Pan-caspase inhibitor Z-VAD-FMK inhibited cell apoptosis induced by TRAIL alone or combined with low-toxicity Embelin, which indicated the cytotoxic effect is mediated by caspase-dependent apoptosis. Although Embelin is an X chromosome-linked inhibitor-of-apoptosis protein (XIAP) inhibitor, an XIAP independent effect on cell death was detected in HL-60 cells exposed to low-toxicity Embelin and TRAIL. Low-toxicity Embelin upregulated DR4 and DR5 expression to enhance TRAIL-induced apoptosis. The sensitizing effects of Embelin on TRAIL-induced apoptosis were markedly attenuated when DR4/DR5 was knocked down. These data suggested that low-toxicity Embelin enhanced TRAIL-induced cell apoptosis through DR4 and DR5 upregulation, indicating that combination of low-toxicity Embelin and TRAIL may become as a potential antileukemia strategy.