Exploring the potential of mindfulness-based therapy in the prevention and treatment of neurodegenerative diseases based on molecular mechanism studies.

Neurodegenerative diseases (ND) have received increasing attention due to their irreversibility, but there is still no means to completely cure ND in clinical practice. Mindfulness therapy (MT), including Qigong, Tai Chi, meditation, and yoga, etc., has become an effective complementary treatment modality in solving clinical and subclinical problems due to its advantages of low side effects, less pain, and easy acceptance by patients. MT is primarily used to treat mental and emotional disorders. In recent years, evidence has shown that MT has a certain therapeutic effect on ND with a potential molecular basis. In this review, we summarize the pathogenesis and risk factors of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), relating to telomerase activity, epigenetics, stress, and the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) mediated inflammatory response, and analyze the molecular mechanism basis of MT to prevent and treat ND, to provide possible explanations for the potential of MT treatments for ND.

Ranunculus ternatus Thunb extract attenuates renal fibrosis of diabetic nephropathy via inhibiting SMYD2.

CONTEXT: Ranunculus ternatus Thunb (Ranunculaceae), (RTT) is used clinically for the treatment of tuberculosis or as tumour adjuvant therapy, but its potential effect on diabetic nephropathy (DN) has not been studied. OBJECTIVE: To investigate the effect of RTT extract in renal fibrosis of DN. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into four groups (n = 12). Diabetes mellitus (DM) mice were induced by streptozotocin (STZ, 55 mg/kg/day) for five consecutive days and treated by RTT extract (2 g/kg). Afterward, blood glucose, HE and Masson staining were assayed. The expression levels of Vimentin, ɑ-SMA, TNF-ɑ, NF-κB p-p65, NF-κB p65, SMYD2, H3K36me3, H3K4me3 were determined by western blots. Firbronectin was respectively assayed by western blot and immunofluorescent staining. RESULTS: RTT extract significantly ameliorated renal injury and renal fibrosis in the renal tissue of STZ-induced diabetic mice as demonstrated by the decreased expression level of Fibronectin (65%), Vimentin and α-SMA (75% & 53%). In addition, the levels of TNF-α (57%), NF-κB p-p65 and NF-κB p65 (35% & 25%) were elevated in the DN mice. Importantly, these were alleviated after RTT extract treatment. Moreover, we observed that the protein levels of SMYD2 (30%), H3K36me3 and H3K4me3 (53% & 75%) were reduced in DN mice after treatment with RTT extract. DISCUSSION AND CONCLUSIONS: RTT extract mediates antifibrotic effects and anti-inflammatory responses in STZ-induced DN mainly through suppressing SMYD2 activation and H3K36me3 and H3K4me3 protein expression. RTT extract might have therapeutic potential against high glucose-induced nephropathy.

Dietary fibers fractionated from gardenia (Gardenia jasminoides Ellis) husk: structure and in vitro hypoglycemic effect.

BACKGROUND: Gardenia (Gardenia jasminoides Ellis) husk rich in dietary fiber is a byproduct of fructus processing, and commonly discarded as waste. The husk was fractionated by sequential extraction into four fractions: water-soluble fiber (W-SF), acid-soluble fiber (Ac-SF), alkali-soluble fiber (Al-SF) and insoluble residue fiber (IRF). The aim of this study was to investigate the differences in structure and in vitro hypoglycemic effect of these fibers. RESULTS: Monosaccharide composition and Fourier transform infrared spectra showed that the major component might be pectin for W-SF and Ac-SF, xylan as well as pectin for Al-SF and cellulose for IRF. These fibers offered excellent water-holding capacity and swelling capacity, except that IRF was only slightly swellable in water. W-SF exhibited significantly higher capacities to adsorb glucose (2.408 mmol g-1 at a glucose concentration of 200 mmol L-1 ) and inhibit α-amylase activity (29.48-49.45% inhibition rate at a concentration of 4-8 mg mL-1 ), probably caused by the higher viscosity and hydration properties; while Ac-SF, Al-SF and IRF (especially Al-SF) were more effective in retarding the glucose diffusion across a dialysis membrane (34.97-41.67% at 20-30 min), which might be attributed to particle size and specific surface area. All the fibers could quench the intrinsic fluorescence of α-amylase to some degree. CONCLUSIONS: Dietary fiber from gardenia husk, especially W-SF, can be used as a potential hypoglycemic ingredient in diabetic functional foods. © 2020 Society of Chemical Industry.

A Systematic Review and Meta-Analysis about the Effect of Bisphosphonates on the Risk of Skeletal-Related Event in Men with Prostate Cancer.

BACKGROUND: Although the adjuvant therapy of bisphosphonates in prostate cancer is effective in improving bone mineral density, it is still uncertain whether bisphosphonates could decrease the risk of Skeletal- Related Event (SRE) in patients with prostate cancer. We reviewed and analyzed the effect of different types of bisphosphonates on the risk of SRE, defined as pathological fracture, spinal cord compression, radiation therapy to the bone, surgery to bone, hypercalcemia, bone pain, or death as a result of prostate cancer. METHODS: A systemic literature search was conducted on PubMed and related bibliographies. The emphasis during data extraction was laid on the Hazard Ratio (HR) and the corresponding 95% Confidence Interval (CI) from every eligible Randomized Controlled Trial (RCT). HR was pooled with the fixed effects model, and preplanned subgroup analyses were performed. RESULTS: 5 RCTs (n = 4651) were included and analyzed finally after screening 51 articles. The meta-analysis of all participants showed no significant decrease in the risk of SRE when adding bisphosphonates to control group (HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536) with low heterogeneity (I2 = 0.0% (d.f. = 4) p = 0.679). There was no significant improvement on SRE neither in the subgroups with Metastases (M1) or Castration-Sensitive Prostate Cancer (CSPC) (respectively HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536, I2 = 0.0% (d.f. = 4) p = 0.679; HR = 0.954, 95% CI = 0.837 - 1.088, p = 0.484, I2 = 0.0% (d.f. = 3) p = 0.534). CONCLUSION: Our study demonstrated that bisphosphonates could not statistically significantly reduce the risk of SRE in patients with prostate cancer, neither in the subgroups with M1 or CSPC.

Effect of bisphosphonates on overall survival in subgroups of patients with prostate cancer.

Adjuvant therapy with bisphosphonates in prostate cancer is effective in improving bone mineral density and thus reducing fractures and skeletal-related events. We analyzed the effect of bisphosphonates on overall survival (OS) in subgroups of patients with prostate cancer. A systematic literature search was conducted of the PubMed database and the bibliographies of related studies. The long-term OS rates were extracted from every eligible trial. The hazard ratio (HR) was pooled with the fixed effects model, and preplanned subgroup analyses were performed. The search yielded 112 articles, of which 10 articles with 13 patient subgroups met the eligibility criteria. The meta-analysis of all 13 subgroups showed that adjuvant bisphosphonate therapy did not significantly improve OS versus the control group (HR = 0.961, 95% CI 0.899-1.026, p = 0.233) with low heterogeneity (I2 = 13.47%, degrees of freedom = 12, p = 0.336). There was no significant improvement in OS with the addition of bisphosphonates in the major subgroup analyses (metastatic (M1) versus non-metastatic, clodronate versus zoledronic acid, castration-sensitive prostate cancer (CSPC) versus castration-refractory prostate cancer). When the subgroups were further divided, adjuvant bisphosphonate therapy significantly improved OS in patients with CSPC + M1 (HR = 0.874, 95% CI 0.778-0.982, p = 0.023; I2 = 0.0%, degrees of freedom = 3, p = 0.579). Our study demonstrated that bisphosphonates do not significantly improve long-term OS in patients with prostate cancer. However, adjuvant bisphosphonate therapy significantly improves OS in the subgroup of patients with CSPC + M1.

Therapeutic Potential of Naringin for Intervertebral Disc Degeneration: Involvement of Autophagy Against Oxidative Stress-Induced Apoptosis in Nucleus Pulposus Cells.

Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but few efficacious medicines have been developed for IDD. Increased nucleus pulposus cells apoptosis is a dominant pathogenesis of IDD and is considered a therapeutic target. Previously, our group proved that autophagy may protect nucleus pulposus cells against apoptosis. As one of the major bioflavonoids of citrus, naringin activates autophagy. Therefore, we hypothesize that naringin may have therapeutic potential for IDD by activating autophagy in nucleus pulposus cells. In this study, we evaluated the effects of naringin on TBHP-induced oxidative stress in nucleus pulposus cells in vitro as well as in puncture-induced rat IDD model in vivo. Our results showed that naringin could reduce the incidence of oxidative stress-induced apoptosis in nucleus pulposus cells and promoted the expression of autophagy markers LC3-II/I and beclin-1. Meanwhile, inhibition of autophagy by 3-MA may partially reverse the anti-apoptotic effect of naringin, indicating that autophagy was involved in the protective effect of naringin in nucleus pulposus cells. Further study showed that autophagy regulation of naringin may be related to AMPK signaling. Also, we found that naringin treatment can regulate the expression of collagen II, aggrecan and Mmp13 to sustain the extracellular matrix. Furthermore, our in vivo study showed that naringin can ameliorate IDD in puncture-induced rat model. In conclusion, our study suggests that naringin can protect nucleus pulposus cells against apoptosis and ameliorate IDD in vivo, the mechanism may relate to its autophagy regulation.