The efficacy of immunosuppressive drugs induction therapy for lupus nephritis: a systematic review and network meta-analysis.

OBJECTIVE: This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN). METHODS: A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I2 was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols. RESULTS: The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile. CONCLUSIONS: Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did' not include results on other adverse events.

Antioxidants stimulate BACH1-dependent tumor angiogenesis.

Lung cancer progression relies on angiogenesis, which is a response to hypoxia typically coordinated by hypoxia-inducible transcription factors (HIFs), but growing evidence indicates that transcriptional programs beyond HIFs control tumor angiogenesis. Here, we show that the redox-sensitive transcription factor BTB and CNC homology 1 (BACH1) controls the transcription of a broad range of angiogenesis genes. BACH1 is stabilized by lowering ROS levels; consequently, angiogenesis gene expression in lung cancer cells, tumor organoids, and xenograft tumors increased substantially following administration of vitamins C and E and N-acetylcysteine in a BACH1-dependent fashion under normoxia. Moreover, angiogenesis gene expression increased in endogenous BACH1-overexpressing cells and decreased in BACH1-knockout cells in the absence of antioxidants. BACH1 levels also increased upon hypoxia and following administration of prolyl hydroxylase inhibitors in both HIF1A-knockout and WT cells. BACH1 was found to be a transcriptional target of HIF1α, but BACH1's ability to stimulate angiogenesis gene expression was HIF1α independent. Antioxidants increased tumor vascularity in vivo in a BACH1-dependent fashion, and overexpressing BACH1 rendered tumors sensitive to antiangiogenesis therapy. BACH1 expression in tumor sections from patients with lung cancer correlated with angiogenesis gene and protein expression. We conclude that BACH1 is an oxygen- and redox-sensitive angiogenesis transcription factor.

The association between Geriatric Nutritional Risk Index and the risk of Invasive Candidiasis in critically ill older adults.

BACKGROUND: Invasive candidiasis is the most common hospital-acquired fungal infection in intensive care units (ICU). The Geriatric Nutritional Risk Index (GNRI) score was developed to evaluate the nutritional status of elderly adults. We aimed to assess the association between the GNRI score and the risk of invasive candidiasis in elderly patients admitted to ICU. METHODS: Hospitalization information of elderly patients with invasive candidiasis was collected retrospectively from Medical Information Mart for Intensive Care (MIMIC) IV and MIMIC-III Clinical Database CareVue subset from 2001 to 2019. The main outcome of this study was the diagnosis of invasive candidiasis in patients. We employed a multivariable Cox regression and propensity score matching to balance the influence of confounding factors on the outcome. Furthermore, we conducted sensitivity analyses by categorizing the GNRI into classes based on thresholds of 98, 92, and 81. RESULTS: A total of 6739 patients were included in the study, among whom 134 individuals (2%) were diagnosed with invasive candidiasis. The GNRI scores of patients with invasive candidiasis upon admission to the ICU were significantly lower, measuring 88.67 [79.26-98.27], compared to the control group with a score of 99.36 [87.98-110.45] (P < 0.001). The results of the multivariable Cox regression analysis demonstrated a strong association between higher GNRI scores and a decreased risk of invasive candidiasis infection (HR: 0.98, 95% CI: 0.97-0.99, P = 0.002). Consistently, similar results were obtained when analyzing the propensity score-matched cohort (HR: 0.99, 95% CI: 0.98-1, P = 0.028). Sensitivity analyses further confirmed a significantly increased risk of invasive candidiasis infection with lower GNRI scores. Specifically, the following associations were observed: GNRI ≤ 98 (HR: 1.83, 95% CI: 1.23-2.72, P = 0.003), GNRI ≤ 92 (HR: 1.68, 95% CI: 1.17-2.4, P = 0.005), 82 ≤ GNRI ≤ 92 (HR: 1.63, 95% CI: 1.01-2.64, P = 0.046), GNRI ≤ 81 (HR: 2.31, 95% CI: 1.44-3.69, P < 0.001). CONCLUSIONS: Lower GNRI score was significantly associated with an increased risk of invasive candidiasis in elderly patients in ICU. Further research is needed to validate whether improving nutrition can prevent invasive candidiasis.

Pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) leads to the activation of RhoGTPases promoting the malignant phenotypes of thyroid cancer.

Thyroid cancer (TC) is one of the most common endocrine system cancers, and its incidence is elevating. There is an urgent need to develop a deeper understanding of TC pathogenesis and explore new therapeutic target for its treatment. This study aimed to investigate the effects of pleckstrin homology and RhoGEF domain containing G4 (PLEKHG4) on the progression of TC. Herein, 29 pairs of TC and adjacent tissues were used to assess the expression of PLEKHG4. A xenograft model of mouse was established by subcutaneously injected with TC cells. Lung metastasis model was established through left ventricular injection. The results revealed that PLEKHG4 was up-regulated in human TC tissues. PLEKHG4 level was correlated with clinicopathological parameters of TC patients. In vitro assays revealed that PLEKHG4 promoted TC cell proliferation, migration, invasion, and epithelial-mesenchymal transformation. Knockdown of PLEKHG4 led to the opposite effects, and the loss of PLEKHG4 enhanced the apoptosis ability and inhibited the stemness properties of TC cells. These findings were further confirmed by the in vivo growth and lung metastasis of TC tumor. Mechanistically, PLEKHG4 promoted the activation of RhoGTPases RhoA, Cdc42, and Rac1. The inhibitors of these RhoGTPases reversed the PLEKHG4-induced malignant phenotypes. Additionally, ubiquitin-conjugating enzyme E2O (UBE2O), a large E2 ubiquitin-conjugating enzyme acted as an ubiquitin enzyme of PLEKHG4, facilitated its ubiquitination and degradation. In conclusion, PLEKHG4, regulated by UBE2O, promoted the thyroid cancer progression via activating the RhoGTPases pathway. UBE2O/PLEKHG4/RhoGTPases axis is expected to be a novel a therapeutic target for TC treatment.

Lipids, lipid-lowering agents, and inflammatory bowel disease: a Mendelian randomization study.

Background: To assess the causal role of lipid traits and lipid-lowering agents in inflammatory bowel disease (IBD). Methods: Univariable mendelian randomization (MR) and multivariable MR (MVMR) analyses were conducted to evaluate the causal association between low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and IBD. Drug-targeted MR analyzed the effects of lipid-lowering drugs on IBD, and network MR was used to analyze potential mediation effects. Results: The levels of HDL-C had an inverse relationship with the risk of Crohn's disease (CD, OR: 0.85, 95% CI: 0.73-0.98, P = 0.024). In MVMR, the inverse relationships were found in all three outcomes. Drug-targeted MR analyses showed that with one-SD LDL-C decrease predicted by variants at or near proprotein convertase subtilisin/kexin type 9 (PCSK9), the OR values of people diagnosed with IBD, ulcerative colitis (UC) and CD were 1.75 (95%CI: 1.13-2.69, P = 0.011), 2.1 (95%CI: 1.28-3.42, P = 0.003) and 2.24 (95%CI: 1.11-4.5, P = 0.024), respectively. With one-SD LDL-C decrease predicted by variants at or near cholesteryl ester transfer protein (CETP), the OR value of people diagnosed with CD was 0.12 (95%CI: 0.03-0.51, P = 0.004). Network-MR showed that HDL-C mediated the causal pathway from variants at or near CETP to CD. Conclusion: Our study suggested a causal association between HDL-C and IBD, UC and CD. Genetically proxied inhibition of PCSK9 increased the risk of IBD, UC and CD, while inhibition of CETP decreased the risk of CD. Further studies are needed to clarify the long-term effect of lipid-lowering drugs on the gastrointestinal disorders.

Colorimetric and visual determination of uric acid based on decolorization of manganese dioxide nanosheet dispersions.

Serum levels of uric acid (UA) play an important role in the prevention of diseases. Developing a rapid and accurate way to detect UA is still a meaningful task. Hence, positively charged manganese dioxide nanosheets (MnO2NSs) with an average latter size of 100 nm and an ultra-thin thickness of below 1 nm have been prepared. They can be well dispersed in water and form stable yellow-brown solutions. The MnO2NSs can be decomposed by UA via redox reaction, leading to a decline of a characteristic absorption peak (374 nm) and a color fading of MnO2NSs solution. On this basis, an enzyme-free colorimetric sensing system for the detection of UA has been developed. The sensing system shows many advantages, including a wide linear range of 0.10-50.0 µmol/L, a limit of quantitation (LOQ) of 0.10 µmol/L, a low limit of detection (LOD) of 0.047 µmol/L (3σ/m), and rapid response without need of strict time control. Moreover, a simple and convenient visual sensor for UA detection has also been developed by adding an appropriate amount of phthalocyanine to provide a blue background color, which helps to increase visual discrimination. Finally, the strategy has been successfully applied to detect UA in human serum and urine samples.

Cauliflower-shaped Pleurotus ostreatus cultivated in an atmosphere with high environmental carbon dioxide concentration.

Commercial aspects, physiological properties, and nutritional characteristics of Pleurotus ostreatus grown under various environmental carbon dioxide concentration ([CO2]e) conditions were assessed. As [CO2]e increased, the activity of antioxidant enzymes (catalase, peroxidase, and superoxide dismutase) in fruiting body increased, activities of succinate dehydrogenase and cytochrome c oxidase were inhibited, and malondialdehyde and adenosine triphosphate (ATP) syntheses were reduced, leading to incomplete development of pilei and stipes, or even absence of pilei. Under high [CO2]e (≥1.00%), fruiting body of P. ostreatus was morphologically altered to assume cauliflower shape. This cultivation condition resulted in high total contents of crude protein, crude fiber, and amino acids, increased levels of umami- and sweet-tasting amino acids, and reduced levels of bitter-tasting amino acids, thus enhancing the flavor of the product. In conclusion, a novel "cauliflower-shaped" mushroom (P. ostreatus) was successfully cultivated at high (≥1.00%) environmental CO2 concentration. The product has a delicious taste and high nutritional value, is relatively easy to transport and store, and has excellent potential for commercial development.

[Surface-enhanced Raman detection of deoxynivalenol allenol in agricultural products].

Fungal toxins are secondary metabolites of fungi. Food is highly susceptible to contamination by various fungal species that produce fungal toxins during production and storage. Fungal toxins can cause either acute or chronic poisoning from long-term, low-dose ingestion. Therefore, fungal toxins have become a topic of international interest as a food safety issue. Deoxynivalenol (DON) is a single-terminal sporam toxin produced predominantly by Fusarium graminae and Fusarium pinkosa. DON is globally one of the most common fungal toxins contaminating grain, food, and feed. Various methods have been applied for screening and detecting DON; however, these methods utilize expensive instruments and entail complex operations, poor repeatability, and low sensitivity. Therefore, the development of a simpler, more rapid, and sensitive sensing technology for DON detection is important for applications within the agriculture and food industry. Recently, surface-enhanced Raman scattering (SERS) has become a rapidly developing spectral analysis technology with unique advantages, including high sensitivity, high throughput, and rapid response rates. Therefore, attempts have been made to apply the SERS technique to detecting DON. However, due to the limitations concerning SERS substrates, the currently established SERS method exhibits serious problems, including low sensitivity and weak anti-interference ability, and cannot meet the requirements of sample detection. Recently, our group has prepared aggregated silver nanoparticles (a-AgNPs/CDs) with high SERS activity by using single-layer carbon-based dots (CDs) as a capping agent. Moreover, the obtained materials (a-AgNPs/CDs) were combined with hydrogel technology to prepare novel hydrogel SERS chips. The obtained SERS chips exhibited several advantages over traditional SERS substrates, such as high sensitivity, long-term stability, improved uniformity, and strong anti-interference capabilities. Herein, a novel SERS method for rapid screening and detection of DON in grains was established using a portable Raman spectrometer based on the developed hydrogel SERS chips. The main experimental conditions were optimized before the SERS detection of DON; this included the optimization of the hydrogel SERS chip soaking temperature and time in the DON solution. It was found that the optimal soaking temperature and time were 40 ℃ and 5 min, respectively. Under the optimal SERS detection conditions, the linear response range of DON was 1-10000 µg/kg (correlation coefficient (R2)=0.9967), and the limit of detection (LOD) was 0.14 µg/kg. Due to the unique pore size structure of the hydrogel, common sugar, protein, oil, pigment, and other interfering substances in the sample matrix were blocked outside the hydrogel. Therefore, only simple extraction was required while detecting complex samples. This method was applied to detecting DON in wheat flour, yielding recoveries of 97.3%-103% with relative standard deviations of 4.2%-5.0%. The established SERS method for DON detection exhibits a broader response range, high sensitivity, good repeatability, rapid response, simple operation, and strong anti-interference capability. This shows that the laboratory-constructed hydrogel SERS chip has excellent potential for rapid screening and detection of biotoxins in food.

Disruption of adipocyte HIF-1α improves atherosclerosis through the inhibition of ceramide generation.

Atherosclerosis is a chronic multifactorial cardiovascular disease. Western diets have been reported to affect atherosclerosis through regulating adipose function. In high cholesterol diet-fed ApoE -/- mice, adipocyte HIF-1α deficiency or direct inhibition of HIF-1α by the selective pharmacological HIF-1α inhibitor PX-478 alleviates high cholesterol diet-induced atherosclerosis by reducing adipose ceramide generation, which lowers cholesterol levels and reduces inflammatory responses, resulting in improved dyslipidemia and atherogenesis. Smpd3, the gene encoding neutral sphingomyelinase, is identified as a new target gene directly regulated by HIF-1α that is involved in ceramide generation. Injection of lentivirus-SMPD3 in epididymal adipose tissue reverses the decrease in ceramides in adipocytes and eliminates the improvements on atherosclerosis in the adipocyte HIF-1α-deficient mice. Therefore, HIF-1α inhibition may constitute a novel approach to slow atherosclerotic progression.

False luminescence of molybdenum disulfide quantum dots from carbon dots.

For the first time, a systematical investigation has been carried out to verify luminescent molybdenum disulfide quantum dots (MoS2 QDs). We found that the well-reported blue fluorescence of the so-called "MoS2 QDs" is mainly originated from the co-present carbon based dots rather than MoS2. Furthermore, the band gap of MoS2 is independent of the lateral size, and it is impossible to obtain luminescent MoS2 QDs by reducing the lateral size.

Bone tumors effective therapy through functionalized hydrogels: current developments and future expectations.

Primary bone tumors especially, sarcomas affect adolescents the most because it originates from osteoblasts cells responsible for bone growth. Chemotherapy, surgery, and radiation therapy are the most often used clinical treatments. Regrettably, surgical resection frequently fails to entirely eradicate the tumor, which is the primary cause of metastasis and postoperative recurrence, leading to a high death rate. Additionally, bone tumors frequently penetrate significant regions of bone, rendering them incapable of self-repair, and impairing patients' quality of life. As a result, treating bone tumors and regenerating bone in the clinic is difficult. In recent decades, numerous sorts of alternative therapy approaches have been investigated due to a lack of approved treatments. Among the novel therapeutic approaches, hydrogel-based anticancer therapy has cleared the way for the development of new targeted techniques for treating bone cancer and bone regeneration. They include strategies such as co-delivery of several drug payloads, enhancing their biodistribution and transport capabilities, normalizing accumulation, and optimizing drug release profiles to decrease the limitations of current therapy. This review discusses current advances in functionalized hydrogels to develop a new technique for treating bone tumors by reducing postoperative tumor recurrence and promoting tissue repair.

Hybridizing Silver Nanoparticles in Hydrogel for High-Performance Flexible SERS Chips.

An ideal surface-enhanced Raman scattering (SERS) substrate should have high sensitivity, long-term stability, excellent repeatability, and strong anti-interference. In the present work, single-layer carbon-based dot (CD)-capped Ag nanoparticle aggregates (a-AgNPs/CDs) with high SERS activity are synthesized and hybridized with a hydrogel to prepare novel hydrogel SERS chips. Benefiting from the unique properties of a-AgNPs/CDs and the hydrogel, the constructed hydrogel SERS chips show excellent performances. Taking crystal violet detection as an example, the hydrogel SERS chips show a detection limit of around 1 × 10-16 mol/L (high sensitivity), maintain above 96.40% of SERS activity even after 14 weeks of storage (long-term stability), and display point-to-point relative standard deviation (RSD) in one chip as low as 1.43% (outstanding repeatability) and RSD in different chips as low as 2.75% (excellent reproducibility). Furthermore, the self-extraction effect of the hydrogel enables the flexible hydrogel SERS chips to be used for analyzing various real samples including soybean milk, juices, and fruits without any complex pretreatment. For instance, the hydrogel SERS chips are able to detect trace thiram and 2-(4-thiazolyl)benzimidazole with the detection limits of 1 and 5 ppb in liquid samples, respectively, and of 1 and 2.5 ng/cm2 on the peel of fruits, respectively. The self-extraction functional flexible SERS chips offer a reliable and convenient platform for the quick detection and on-site monitoring of chemical contaminants.

Hybridizing aggregated gold nanoparticles with a hydrogel to prepare a flexible SERS chip for detecting organophosphorus pesticides.

Surface enhanced Raman scattering (SERS) is an ultrasensitive analytic technique. However, the application of SERS in quantitative analysis usually suffers from poor reliability due to the limitations of currently developed SERS substrates. In the present work, aggregated gold nanoparticles (a-AuNPs) fabricated by Ca2+-mediated assembly are dispersed in polyvinyl alcohol solution to prepare a novel hydrogel SERS chip through a physical crosslinking method. Taking advantage of the uniform distribution of SERS active a-AuNPs in the three-dimension hydrogel and the excellent barrier effect of hydrogel towards oxygen and macromolecules, the obtained hydrogel SERS chips show many outstanding advantages including high sensitivity, good repeatability, long-term stability, and a robust anti-interference ability. These advantages enable hydrogel SERS chips to be used to quantitatively analyse some complex samples without complex sample preprocessing. As a model, the hydrogel SERS chips are used for the detection of triazophos and phosmet in orange samples. The good recoveries suggest good applicability of the hydrogel SERS chips in food safety detection. This work provides a reliable and convenient platform for the quick detection and on-site monitoring of chemical contaminants and would promote greatly the performance of SERS techniques in quantitative analysis.

Open Search-Based Proteomics Reveals Widespread Tryptophan Modifications Associated with Hypoxia in Lung Cancer.

The tryptophan residue has a large hydrophobic surface that plays a unique role in the folded protein conformation and functions. Tryptophan modifications are presumably to be readily detected in proteins due to the vulnerability of the indole structure to electrophilic attacks. In this study, we report a systematic identification of sequence variations at tryptophan, termed tryptophan variants, from the proteome of patients with nonsmall cell lung cancer (NSCLC). Using shotgun proteomics and a modified open search algorithm, 25 tryptophan variants on 2481 sites in over 858 proteins were identified. Among these, 6 tryptophan variants are previously identified, 15 are newly annotated, and 4 are still unknown, most of which are involved in the cascade of oxidation in the blood microparticle. Remarkably, Trp313 of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was up-oxidized whereas Trp16 and Trp38 of hemoglobin (HBB) were down-oxidized in NCSLC tissues. The results were further supported by an independent cohort of 103 lung adenocarcinoma samples, reflecting a negative feedback and potential detoxification mechanism against tumor glycolysis and hypoxia. Overall, the study reports a quick approach to explore tryptophan variants at the proteomic scale. Our findings highlight the predominant role of tryptophan oxidation in regulating the redox balance of cancer cells and its potential role as prognostic biomarker for patients with NSCLC.

[Research Progress on Vector Flow Imaging of Cardiac Ultrasound].

Echocardiogram is vital for the diagnosis of cardiac disease. The heart has complex hemodynamics requiring an advanced ultrasound imaging mode. Cardiac ultrasound vector flow imaging is capable of measuring the actual magnitude and direction of the blood flow velocity, obtaining the quantitative parameters of hemodynamics, and then providing more information for clinical research and diagnosis. This study mainly reviewed several different vector flow imaging techniques for cardiac flow and presented the implementation difficulties, and proposed a diverging wave based high frame rate cardiac ultrasound vector flow imaging. The study discussed the limitation of current ultrasound technology used in the cardiac flow measurement, analyzed and demonstrated the specific reasons for these implementation difficulties and the potential future development.

Role of FSCN1 in the tumor microenvironment of lung squamous cell carcinoma.

Tumor microenvironment (TME) regulated the development of the Lung squamous cell carcinoma (LUSC). To know more about the LUSC, this study tried to figure the role of fscin actin-bundling protein 1 (FSCN1) in the TME. We identified the FSCN1 as the hub immune gene in LUSC, with the use of weighted gene co-expression network analysis (WGCNA) and the Human Protein Atlas. Furthermore, we verified the higher expression of FSCN1 in LUSC compared with the normal tissues by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry. We then explored the associations among FSCN1, immune infiltrations, and inflammatory factors with the use of Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor IMmune Estimation Resource (TIMER). As a result, the expressions of FSCN1 was negatively related to the immune infiltrations, and positively related to the expressions of IL1A, IL1B, TGFB1 and TGFA. Moreover, we used the single-cell RNA-sequencing (scRNA-seq) data of LUSC to figure out the expressions level of FSCN1, IL1A, IL1B, TGFB1 and TGFA in the different cell type's of the TME. Finally, through the cytological experiments, we found that FSCN1 affected by TGFB1 contributes to the proliferation, anti-apoptotic effect, migration and invasion of the LUSC cells. In summary, this study Identified FSCN1 as the potential therapeutic target of LUSC, and reveals a complicated immune and inflammatory net in the TME.

Efficacy of flaxseed oil compared with fish oil supplementation in the treatment of coronary heart disease: a retrospective study.

Background: Many studies have demonstrated the beneficial effects of omega-3 fatty acids in animal models and human diseases. Compared with commonly used fish oil, flaxseed oil has better palatability. However, the relative efficacy of the two types of oil on the cardiovascular health of type 2 diabetes mellitus (T2DM) patients with coronary heart disease (CHD) is unclear. Methods: This was a retrospective study based on the prospectively maintained database of Hubei Provincial Hospital of Traditional Chinese Medicine. Patients meeting the inclusion criteria were enrolled and then divided into two groups: the flaxseed oil group received 1,000 mg flaxseed oil, which contains 400 mg of α-Linolenic acid, as their omega-3 fatty acid source; the fish oil group received 1,000 mg of fish oil, which contains 250 mg of eicosapentaenoic acid and 150 mg of docosahexaenoic acid. The primary outcome was cardiovascular risk biomarker changes between the two groups. P values less than 0.05 were considered statistically significant. Results: A total of 120 patients were enrolled in the present study: 60 in the flaxseed oil group and 60 in the fish oil group. After a median follow-up of 10.0 weeks (95% CI: 8.4-11.6 weeks), flaxseed oil was found to be significantly better at reducing serum insulin levels and high-sensitivity C-reactive protein (hs-CRP) levels than fish oil (P=0.03 and P=0.02, respectively). The effects of flaxseed oil and fish oil on homeostatic model assessment for insulin resistance (HOMA-IR), fasting plasma glucose (FPG); body weight, and body mass index (BMI) were found to be similar. Moreover, patients who received flaxseed oil tended to have a better overall survival than those who received fish oil, although the difference was not statistically significant (P=0.067). Conclusions: Compared with fish oil, flaxseed oil was more effective in reducing serum insulin levels and hs-CRP levels for T2DM patients with CHD. For these patients, flaxseed oil might become a novel choice.

State of the art of bone biomaterials and their interactions with stem cells: Current state and future directions.

BACKGROUND: There has been a rapid increase in bone tissue regeneration since the concept of "tissue engineering." Stem cell-based biomaterials have revolutionized the field of tissue regeneration. Biomaterials play an essential part in bone regeneration through their crucial substratum for cell differentiation, cohesion, and proliferation by manipulating cells. Numerous studies have been carried out in order to create a biomaterial with diverse biological and physical characteristics. Furthermore, they developed a cell microenvironment with the desired pore magnitude to stimulate stem cells to transform them from artificial to biological microenvironments. PURPOSE AND SCOPE: The current review aims to give a comprehensive overview of stem cells and biomaterials in bone tissue regeneration. SUMMARY: Initially, bone biology and its interaction with stem cells and biomaterials are briefly explained. Following that, the behavior and mechanism of biomaterials influencing the stem cells during bone tissue regeneration are emphasized. Lastly, the future outlook for tackling the current challenges for designing biomaterials/stem cell materials for bone tissue engineering (TE) is discussed. CONCLUSION: Compatible biomaterial for bone regeneration requires evaluating the structure, matrix, composition, flexibility, and nature of native bone tissue defects. The concept of TE offers a platform for designing biologically, physically, and chemically biocompatible biomaterials for stem cells to proliferate and differentiate. Currently, stem cells are increasingly used for TE with a promising outcome due to their self-renewal and differentiation potential. Furthermore, they can secrete biological-active compounds and modulate the fate and behavior of other cells in native tissues. Bone TE may flourish more rapidly and efficiently using stem cells.

The role of long non-coding RNAs and circular RNAs in bone regeneration: Modulating miRNAs function.

Although bone is a self-healing organ and is able to repair and restore most fractures, large bone fractures, about 10%, are not repairable. Bone grafting, as a gold standard, and bone tissue engineering using biomaterials, growth factors, and stem cells have been developed to restore large bone defects. Since bone regeneration is a complex and multiple-step process and the majority of the human genome, about 98%, is composed of the non-protein-coding regions, non-coding RNAs (ncRNAs) play essential roles in bone regeneration. Recent studies demonstrated that long ncRNAs (lncRNAs) and circular RNAs (circRNAs), as members of ncRNAs, are widely involved in bone regeneration by interaction with microRNAs (miRNAs) and constructing a lncRNA or circRNA/miRNA/mRNA regulatory network. The constructed network regulates the differentiation of stem cells into osteoblasts and their commitment to osteogenesis. This review will present the structure and biogenesis of lncRNAs and circRNAs, the mechanism of bone repair, and the bone tissue engineering in bone defects. Finally, we will discuss the role of lncRNAs and circRNAs in osteogenesis and bone fracture healing through constructing various lncRNA or circRNA/miRNA/mRNA networks and the involved pathways.