Functional foods and dietary supplements in the management of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Objective: In this systematic review and meta-analysis, we aimed to clarify the overall effects of functional foods and dietary supplements in non-alcoholic fatty liver disease (NAFLD) patients. Methods: Randomized controlled trials (RCTs) published in PubMed, ISI Web of Science, Cochrane library, and Embase from January 1, 2000 to January 31, 2022 were systematically searched to assess the effects of functional foods and dietary supplements in patients with NAFLD. The primary outcomes were liver-related measures, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic fibrosis and steatosis, while the secondary outcomes included body mass index (BMI), waist circumference (WC), triacylglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). These indexes were all continuous variables, so the mean difference (MD) was used for calculating the effect size. Random-effects or fixed-effects models were used to estimate the mean difference (MD). The risk of bias in all studies was assessed with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. Results: Twenty-nine articles investigating functional foods and dietary supplements [antioxidants (phytonutrients and coenzyme Q10) = 18, probiotics/symbiotic/prebiotic = 6, fatty acids = 3, vitamin D = 1, and whole grain = 1] met the eligibility criteria. Our results showed that antioxidants could significantly reduce WC (MD: -1.28 cm; 95% CI: -1.58, -0.99, P < 0.05), ALT (MD: -7.65 IU/L; 95% CI: -11.14, -4.16, P < 0.001), AST (MD: -4.26 IU/L; 95% CI: -5.76, -2.76, P < 0.001), and LDL-C (MD: -0.24 mg/dL; 95% CI: -0.46, -0.02, P < 0.05) increased in patients with NAFLD but had no effect on BMI, TG, and TC. Probiotic/symbiotic/prebiotic supplementation could decrease BMI (MD: -0.57 kg/m2; 95% CI: -0.72, -0.42, P < 0.05), ALT (MD: -3.96 IU/L; 95% CI: -5.24, -2.69, P < 0.001), and AST (MD: -2.76; 95% CI: -3.97, -1.56, P < 0.0001) levels but did not have beneficial effects on serum lipid levels compared to the control group. Moreover, the efficacy of fatty acids for treating NAFLD was full of discrepancies. Additionally, vitamin D had no significant effect on BMI, liver transaminase, and serum lipids, while whole grain could reduce ALT and AST but did not affect serum lipid levels. Conclusion: The current study suggests that antioxidant and probiotic/symbiotic/prebiotic supplements may be a promising regimen for NAFLD patients. However, the usage of fatty acids, vitamin D, and whole grain in clinical treatment is uncertain. Further exploration of the efficacy ranks of functional foods and dietary supplements is needed to provide a reliable basis for clinical application. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier: CRD42022351763.

Clinical and genetic investigation in patients with permanent congenital hypothyroidism.

BACKGROUND: Permanent congenital hypothyroidism (CH) is usually a more severe type of CH. However, the molecular etiology and clinical features of permanent CH remain unclear. METHODS: We recruited 42 patients who were diagnosed with CH and followed-up after diagnosis. Demographic information and data at diagnosis and treatment were recorded. Genetic analyses were performed using whole exome sequencing. Based on the presence or absence of variants and differences in clinical features, we grouped the study participants and analyzed their characteristics. RESULTS: A total of 29 patients (69.0 %) were identified as having variants potentially related to their disease. Among the 24 patients with normal-sized thyroid gland-in-situ (GIS) or goiter, 23 (95.8 %, P < 0.001) had variants. This is compared to 18 patients with thyroid dysgenesis (TD), of which six (33.3 %) had genetic variants. We detected 55 variants in six genes, the most frequently mutated gene being DUOX2 (70.9 %). Biallelic DUOX2 variants were detected in 14 of 24 (58.3 %) GIS or goiter patients. Compared to the cases with variants, the L-T4 dose at 2 and 3 years of age and current dose were higher in the unmutated cases. At 2 years of age, patients with TD required higher doses of L-T4 supplementation. Patients with DUOX2 variants showed lower doses of L-T4 being required at 2 and 3 years of age and current. Furthermore, patients with GIS or goiter with DUOX2 variants showed lower doses of L-T4. CONCLUSIONS: Patients with CH, whether TD or GIS or goiter, are at risk of developing a permanent condition. Compared with patients with TD, the detection of variants was higher in patients with GIS or goiter. The most frequently mutated gene was DUOX2, with a biallelic type. Patients with TD required higher doses of L-T4 supplementation with age, whereas those patients with the DUOX2 variant required relatively lower doses.

Ononin ameliorates inflammation and cartilage degradation in rat chondrocytes with IL-1ß-induced osteoarthritis by downregulating the MAPK and NF-κB pathways.

BACKGROUND: Osteoarthritis (OA) treatment aims to improve inflammation and delay cartilage degeneration. However, there is no effective strategy presently available. Ononin, a representative isoflavone glycoside component extracted from natural Chinese herbs, exerts anti-inflammatory and proliferative effects. However, the therapeutic effect of ononin on chondrocyte inflammation remains unclear. METHODS: In this study, we explored the therapeutic effect and potential mechanism of ononin in OA by establishing an interleukin-1 beta (IL-1ß)-induced chondrocyte inflammation model. RESULTS: Our results verified that ononin alleviated the IL-1ß-induced decrease in chondrocyte viability, attenuated the overexpression of the inflammatory factors tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and simultaneously inhibited the expression of cartilage extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteinase-13 (MMP-13). Furthermore, the decomposition of Collagen II protein could be alleviated in the OA model by ononin. Finally, ononin improved chondrocyte inflammation by downregulating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signalling pathways. CONCLUSION: Our findings suggested that ononin could inhibit the IL-1ß-induced proinflammatory response and ECM degradation in chondrocytes by interfering with the abnormal activation of the MAPK and NF-κB pathways, indicating its protective effect against OA.

[Spinal transcription factor GATA4 mediated adenosine A1 receptor activation contributes to electroacupuncture analgesia in neuropathic pain rats].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on pain behaviors and expression of spinal transcription factor GATA-binding Protein 4 (GATA4) and adenosine A1 receptor in neuropathic pain rats, so as to explore its mechanism underlying pain relief. METHODS: The present study includes 2 parts. In the first part, 18 SD rats were randomly divided into control, adenovirus short-hairpin interference RNA for GATA4 (AV-shGATA4 RNA) and adenovirus empty vector (AV-control short-hairpin RNA, AV-shCTRL) groups, with 6 rats in each group. The expression of GATA4 protein in the lumbar spinal cord (L4-L6) was detected to evaluate the transfection efficiency of AV-shGATA4 RNA (silencing GATA4 expression). In the second part, thirty SD rats were randomly divided into 5 groups, namely sham operation, CCI model, EA, EA+AV-shGATA4 RNA, and EA+AV-shCTRL groups, with 6 rats in each group. The neuropathic pain model was established by chronic constriction injury (CCI) of the right sciatic nerve. On the 7th day following modeling, EA was applied to the right "Zusanli"(ST36) and "Taichong"(LR3) (1 mA，2 Hz /100 Hz) for 30 min. Rats of the EA+AV-shGATA4 RNA and EA+AV-shCTRL groups received intrathecal injection of AV-shGATA4 RNA and AV-shCTRL(1×1011 PFU/mL，10 µL)at the spinal L4-L6 segments, separately, 48 h before EA intervention. The mechanical pain threshold and thermal pain threshold of the affected limb were detected before molding, 7 days following molding and 60 min after EA. The expressions of adenosine A1 receptor and GATA4 protein in the spinal cord (L4-L6) were detected by Western blot. RESULTS: Outcomes of the first part showed that compared with the control group, no significant changes were found in the mechanical and thermal pain thresholds in both AV-shCTRL and AV-shGATA4 RNA groups and in the expression of spinal GATA4 protein of the AV-shCTRL group (P＞0.05). The expression of spinal GATA4 protein of the AV-shGATA4 RNA group was significantly lower than that of the AV-shCTRL group (P<0.05). In the second part of the study, before CCI modeling, there were no significant differences among the five groups in the mechanical and thermal pain thre-sholds (P> 0.05). On the 7th day following modeling, the mechanical and thermal pain thresholds were significantly lowered in compa-rison with their own pre-modeling of each group and with the sham operation group (P<0.05). At 60 min after EA and compared with the model group, the mechanical and thermal pain thresholds were significantly increased in both the EA and EA+AV-shCTRL groups (P<0.05) but not in the EA+AV-shGATA4 RNA group (P>0.05), suggesting a critical involvement of GATA4 in EA analgesia. The expression levels of adenosine A1 receptor and GATA4 protein were significantly increased in the model group than in the sham operation group (P<0.05), and considerably further up-regulated in both EA and EA+AV-shCTRL groups (P< 0.05), rather than in the EA+AV-shGATA4 RNA group (P>0.05), suggesting that the effects of EA in up-regulating the expression of A1 receptor and GATA4 were eliminated after silencing GATA4 protein. CONCLUSION: EA of ST36 and LR3 can relieve pain by increasing the expression of adenosine A1 receptor of the lumbar spinal cord in neuropathic pain rats, which is probably mediated by GATA4 protein.

Repair of osteonecrosis of the femoral head : 3D printed Cervi cornus Colla deproteinized bone scaffolds.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common joint disease and a major cause of morbidity. OBJECTIVE: In this study Cervi cornus Colla (CCC) deproteinized bone scaffolds were designed and three dimensional (3D)-printed for the repair of ONFH in rats. MATERIAL AND METHODS: The CCC-deproteinized bone scaffolds were 3D-printed using polycaprolactone mixed with the CCC-deproteinized bone powder. The scaffolds were viewed under a scanning electron microscope and subjected to compression analysis. Osteoblasts were isolated from rats and coated onto the scaffolds. Cell proliferation assays were performed with the MTT (3­[4,5-dimethylthiazole­2]-2,5-diphenyltetrazolium bromide) kit from Promega. An ONFH was induced in rats and a CCC-deproteinized bone scaffold was implanted into the necrotic femoral head. General observations, X­ray imaging, and pathological examination of the femoral head were performed to evaluate the treatment of ONFH in the rats. RESULTS: The scaffolds were porous with a mean pore diameter of 315.70 ± 41.52 nm and a porosity of 72.86 ± 5.45% and exhibited favorable mechanical properties and degradation. In vitro assays showed that osteoblasts accumulated in the pores and adhered to the scaffolds. The CCC-deproteinized bone scaffolds enhanced the proliferation of osteoblasts. The in vivo experiments revealed that the general observation score of rats in the CCC-scaffold implanted group was significantly higher than that in the control group. The X­ray images showed significant alleviation of ONFH in the CCC-deproteinized bone scaffold implanted rats. The femoral heads of rats in the treatment group showed less destruction or ossification of cartilage cells, few bone cement lines, very little necrosis or irregularities on the cartilage surface and only a small amount of inflammatory cell infiltration in the medullary cavity. CONCLUSION: These results suggest that CCC-deproteinized bone scaffold implants facilitated the repair of ONFH in rats. This research provides a new therapeutic approach for the repair of early and mid-term ONFH.

[Safety evaluation of Sophora tonkinensis and risk control].

The aim is to systemically review and evaluate the safety of Sophora tonkinensis from the literature on the herbal origin, toxicity record in modern literature and toxicological studies and publications in recent years. By systematic review and analysis, the results showed that its toxicity mainly involved the nervous system, the digestive system and the respiratory system, and respiratory failure may be the direct cause of death. The main symptoms included headache, dizziness, vomiting, nausea, abdominal pain, limbs weakness, palpitation, and chest distress; as well as pale complexion, limbs trembling, convulsions, chills, high heart rate, fall of blood pressure, shock, and respiratory failure to death in severe cases. High dose and long term medication may cause serious brain damage, especially in adolescents and children. The authors have proposed to use rationally under guidance of physician and strictly according to the dosage recommended by pharmacopoeia. The patients shall not be credulous about the folk prescriptions and test recipes to use it for,prevention of colds and treatment of sore throat at will. In addition, the researches on the conventional treatment methods for S. tonkinensis poisoning, the toxic substance basis, and toxicity mechanism shall be strengthened in further studies. These efforts will play important role in exerting the drug effect and avoiding side effect.

Curcumin, a potential therapeutic candidate for retinal diseases.

Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases.

Heterologous expression of human costimulatory molecule B7-2 and construction of B7-2 immobilized polyhydroxyalkanoate nanoparticles for use as an immune activation agent.

BACKGROUND: Costimulation of T cells via costimulatory molecules such as B7 is important for eliciting cell-mediated antitumor immunity. Presenting costimulation molecules by immobilizing recombinant B7 on the surface of nanovectors is a novel strategy for complementary therapy. Polyhydroxyalkanoates (PHAs) are a family of biodegradable, non-toxic, biocompatible polyesters, which can be used as a nonspecific immobilizing matrix for protein presentation. Recombinant protein fusion with PHA granule binding protein phasin (PhaP) can be easily immobilized on the surface of PHA nanoparticles through hydrophobic interactions between PhaP and PHA, and therefore provides a low-cost protein presenting strategy. RESULTS: In this study, the extracellular domain of the B7-2 molecule (also named as CD86) was fused with PhaP at its N-terminal and heterogeneously expressed in recombinant Escherichia coli strain BL21 (DE3). The purified B7-2-PhaP protein was immobilized on the surface of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)-based nanoparticles. Loading of 240 µg (3.2 pMol) of B7-2-PhaP protein per mg nanoparticles was achieved. Immobilized B7-2-PhaP on PHBHHx nanoparticles induced T cell activation and proliferation in vitro. CONCLUSIONS: A PHA nanoparticle-based B7-2 costimulation molecule-presenting system was constructed. The PHA-based B7 presenting nanosystem provided costimulation signals to induce T cell activation and expansion in vitro. The B7-2-PhaP immobilized PHA nanosystem is a novel strategy for costimulation molecule presentation and may be used for costimulatory molecule complementary therapy.

[Effects of injecting adenosine A1 receptor agonist into baihui (GV20) on the cerebral cortex in ischemia/reperfusion injury model rats].

OBJECTIVE: To investigate the effects of injecting adenosine A1 receptor agonist (CCPA) into Baihui (GV20) on the cerebral cortex induced by the ischemia/reperfusion of middle cerebral artery occlusion (MCAO) in rats. METHODS: Twenty-four SD rats were randomly divided into four groups, i. e., the sham-operation group, the model group, the DMSO group, and the CCPA group. The MCAO model was established by thread embolism method. At the moment of ischemia/reperfusion, the rats in DMSO group and the CCPA group were injected with DMSO (20 microL) and CCPA (0.1 mmol) 20 microL into Baihui respectively. The rats' behavior, the histomorphology of ischemic penumbra in the cerebral cortex, the expressions of Bcl-2 protein, and the apoptosis rate of neurocytes were assessed. RESULTS: Compared with the model group and the DMSO group, the rats' behavior were markedly improved in the CCPA group (P<0.05). No obvious karyopyknosis and cytoplasm empty dye of neurons appeared. The Bcl-2 expressions in rats' cerebral cortex obviously increased (P<0.01). The apoptosis number of neurons obviously decreased (P<0.01). CONCLUSIONS: Injecting CCPA into Bahui improved the rats' behavior and histomorphology in the ischemic penumbra, elevated the expressions of Bcl-2 protein, and reduced the neurons apoptosis rate in the ischemic penumbra. It alleviated the cerebral ischemia-reperfusion injury. Therefore, it could be taken as a new treatment method.

[Determination of sinigrin in semen Thlaspi from Sichuan and Tibet using near infrared diffuse reflectance spectroscopy].

The objective of the present study was to develop a method for the determination of sinigrin in semen Thlaspi from Sichuan using near infrared diffuse reflectance spectroscopy. Near infrared spectra (NIR) in the region of 7,502.1-5,446.2 cm(-1) were recorded for the 246 semen Thlaspi samples containing sinigrin in the content of 1.962%-3.917%. Calibration models were established using the PLS (partial least squares). Different spectra pretreatment methods were compared. The study showed that spectral information can be extracted thoroughly by minimum and maximum normalization pretreatment methods. In this calibration model, the correlation coefficient (R2) was 0.9280, the SEC (standard deviation of the calibration sets) was 0.314 and the SEP (standard deviation of the prediction sets) was 0.388. Results indicated that near infrared diffuse reflectance spectroscopy method can be used to rapidly analyze the valid component in traditional Chinese medicine, and also can be used in the quality control of traditional Chinese medicine.