Vitamin D delays intervertebral disc degeneration and improves bone quality in ovariectomized rats.

Known to be involved in bone-cartilage metabolism, Vitamin D (VD) may play a role in human's disc pathophysiology. Given that postmenopausal women are prone to suffer VD deficiency and intervertebral disc degeneration (IDD), this study is intended to investigate whether VD can delay IDD in ovariectomized rats by improving bone microstructure and antioxidant stress. Female Sprague-Dawley rats were randomly allocated into four groups: sham, oophorectomy (OVX)+VD deficiency (VDD), OVX, and OVX+VD supplementation (VDS). In vivo, after a 6-month intervention, imaging and pathology slice examinations showed that IDD induced by OVX was significantly alleviated in VDS and deteriorated by VDD. The expressions of aggrecan and Collagen II in intervertebral disc were reduced by OVX and VDD, and elevated by VDS. Compared with the OVX+VDD and OVX group vertebrae, OVX+VDS group vertebrae showed significantly improved endplate porosity and lumbar bone mineral density with increased percent bone volume and trabecular thickness. Furthermore, 1α,25(OH)2D3 restored the redox balance (total antioxidant capacity, ratio of oxidized glutathione/glutathione) in the disc. The cocultivation of 1α,25(OH)2D3 and nucleus pulposus cells (NPCs) was conducted to observe its potential ability to resist excessive oxidative stress damage induced by H2O2. In vitro experiments revealed that 1α,25(OH)2D3 reduced the senescence, apoptosis, and extracellular matrix degradation induced by H2O2 in NPCs. In conclusion, VDS exhibits protective effects in OVX-induced IDD, partly by regulating the redox balance and preserving the microstructure of endplate. This finding provides a new idea for the prevention and treatment of IDD.

α-Ketoglutaric acid ameliorates intervertebral disk degeneration by blocking the IL-6/JAK2/STAT3 pathway.

Intervertebral disk degeneration (IVDD) is the major cause of low back pain. Alpha-ketoglutaric acid (α-KG), an important intermediate in energy metabolism, has various functions, including epigenetic regulation, maintenance of redox homeostasis, and antiaging, but whether it can ameliorate IVDD has not been reported. Here, we examined the impacts of long-term administration of α-KG on aging-associated IVDD in adult rats. In vivo and in vitro experiments showed that α-KG supplementation effectively ameliorated IVDD in rats and the senescence of nucleus pulposus cells (NPCs). α-KG supplementation significantly attenuated senescence, apoptosis, and matrix metalloproteinase-13 (MMP-13) protein expression, and it increased the synthesis of aggrecan and collagen II in IL-1ß-treated NPCs. In addition, α-KG supplementation reduced the levels of IL-6, phosphorylated JAK2 and STAT3, and the nuclear translocation of p-STAT3 in IL-1ß-induced degenerating NPCs. The effects of α-KG were enhanced by AG490 in NPCs. The underlying mechanism may involve the inhibition of JAK2/STAT3 phosphorylation and the reduction of IL-6 expression. Our findings may help in the development of new therapeutic strategies for IVDD.NEW & NOTEWORTHY Alpha-ketoglutaric acid (α-KG) exerted its protective effect on nucleus pulposus cells' (NPCs) degeneration by inhibiting the senescence-associated secretory phenotype and extracellular matrix degradation. The possible mechanism may be associated with negatively regulating the JAK2/STAT3 phosphorylation and the decreased IL-6 expression, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK2/STAT3 pathway.

Association Between Poor Nutritional Status and Increased Risk for Subsequent Vertebral Fracture in Elderly People with Percutaneous Vertebroplasty.

Background: The relationship between a poor nutritional state and the risk of fractures has not been investigated. This study aimed to investigate the ability of the Controlling Nutritional Status (CONUT) and Geriatric Nutritional Risk Index (GNRI) to predict the incidence of subsequent vertebral fracture (SVF) after percutaneous vertebroplasty (PVP). Methods: A total of 307 women and 138 men over 50 years old who underwent PVP for osteoporotic vertebral compression fracture (OVCF) were included. Blood biochemical indexes, body mass index (BMI), bone mineral density (BMD), physical function, and muscle strength were measured at baseline. Cox regression analysis was used to determine whether nutritional state was an independent predictor for SVF. Results: During follow-up, 35 (25.4%) men and 85 (27.7%) women suffered SVF. Patients with SVF had lower BMI, serum albumin levels, GNRI scores, grip strength, lumbar BMD, and Short-Physical Performance Battery (SPPB) scores and higher fall rates and CONUT scores (P < 0.05). Compared with normal nutrition, mild malnutrition was associated with higher risk for SVF (women: HR 2.37, p=0.001, men: HR 2.97, p=0.021 by GNRI; women: HR 2.36, p=0.005, men: HR 3.62, p=0.002 by CONUT) after adjusting for confounding factors. Those with moderate-severe malnutrition also had a higher risk of SVF. Kaplan-Meier analysis showed that poor nutrition state was significantly associated with lower SVF-free survival (P<0.05). The area under curve (AUC) for predicting SVF was 0.65 and 0.73 for the GNRI and 0.67 and 0.66 for the CONUT in men and women, respectively. Conclusion: GNRI and CONUT are simple and effective tools for predicting SVF in patients undergoing PVP. Health management and nutrition supplement after PVP is a potentially effective prevention strategy against SVF.

Relationship between Vitamin D and Nonspecific Low Back Pain May Be Mediated by Inflammatory Markers.

BACKGROUND: Vitamin D deficiency has been linked to nonspecific low back pain (Ns-LBP); however, the role of inflammation as a possible mediator between vitamin D levels and Ns-LBP is not well understood. OBJECTIVE: To explore the mediating effects of inflammatory markers on the relationship between vitamin D levels and pain outcomes. STUDY DESIGN: A retrospective study. SETTING: Department of Spinal Surgery of a hospital affiliated to a medical university. METHODS: In this cross-sectional study, we selected patients with non-specific acute low back pain (Ns-ALBP, n = 60) and non-specific chronic low back pain (Ns-CLBP, n = 78), as well as 60 people without Ns-LBP as controls, from January 2018 to January 2019. Serum 25(OH)D and inflammatory marker levels were examined. Regression and causal mediation analysis were used to evaluate the mediating effects of inflammatory markers on the association between vitamin D and pain. RESULTS: Mean serum concentrations of vitamin D in the control, Ns-ALBP, and Ns-CLBP groups were 25.70 ± 10.04, 21.44 ± 8.46 and 18.25 ± 8.05 ng/mL, respectively (P < 0.001). After adjustment for clinical factors, vitamin D deficiency was associated with Ns-LBP (P < 0.05); however, when the interleukin 6 (IL-6) level was added to the multivariable models, the association was no longer significant in Ns-CLBP patients. Mediation analysis estimated the overall mediated effect as -0.461 (P < 0.001) in Ns-CLBP patients, and the intermediary effect of IL-6 was 0.045. LIMITATIONS: A retrospective study may include inevitable bias. More sensitive biomarkers were not investigated in this study. Pain intensity evaluation using the visual analogue scale is inevitably subjective. CONCLUSION: Patients with Ns-LBP had lower vitamin D and higher inflammatory marker levels. This association between hypovitaminosis D and Ns-CLBP may be mediated by IL-6. Therefore, large-scale clinical trials are warranted to investigate the clinical efficacy of vitamin D supplementation for decreasing inflammation and relieving Ns-LBP.

Does vitamin D status influence lumbar disc degeneration and low back pain in postmenopausal women? A retrospective single-center study.

OBJECTIVE: To investigate the relationship between serum vitamin D concentration and lumbar disc degeneration (LDD) in postmenopausal women and the epidemiologic factors affecting low back pain (LBP). METHODS: Between July 2017 and December 2018, 232 participants were retrospectively enrolled. Serum concentrations of bone turnover markers were measured using electrochemiluminescence assays. Disc degeneration was evaluated using the Pfirrmann grading system. Other variables were assessed using relevant questionnaires. RESULTS: The mean age of the women was 65.6 ±â€Š10.1 and their serum 25(OH)D concentrations were 19.38 ±â€Š9.21 ng/mL. The prevalences of severe vitamin D deficiency (<10 ng/mL) and normal status (>30 ng/mL) were 12.9% and 12.5%, respectively. The severely deficient group had higher visual analog scale (VAS) scores for LBP (P = 0.002) and lower bone mineral density T scores (P = 0.004) than the other groups. Lower 25(OH)D concentration (<10 ng/mL) was significantly associated with more severe LDD in the lumbosacral region (L4-S1, L1-S1, P < 0.05), but less so in the upper lumbar region. There was an inverse relationship between vitamin D concentration and the severity of disc degeneration (L2-L3, L4-S1, L1-S1, P < 0.05). After adjustment for confounding factors, smoking, vitamin D deficiency, lack of vitamin D supplementation, high body mass index, and low bone mineral density T score were associated with higher incidence of moderate-to-severe pain in postmenopausal women (P < 0.05). CONCLUSIONS: Vitamin D deficiency is associated with LDD and LBP in postmenopausal women. Specifically, a serum vitamin D concentration < 10 ng/mL is a marker of severe LDD and LBP. Smoking, severe vitamin D deficiency, lack of vitamin D supplementation, high body mass index, and osteoporosis are associated with a higher prevalence of moderate-to-severe pain.

Effects of different treatments on patients with osteoporotic fracture after percutaneous kyphoplasty / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate effects of different treatments on patients with osteoporotic vertebral fracture after percutaneous kyphoplasty in pain and function.</p><p><b>METHODS</b>From March 2010 to March 2012,138 patients (165 vertebrae) with thoracic and lumbar vertebral osteoporotic fracture were randomly divided into three groups (control group, treatment group and comprehensive group), 46 cases in each group, and all patients were treated by PKP. Control group were treated with calcium and calcitriol after operation, treatment group added salmon calcitonin see calcimar based on control group, comprehensive group added incrementality waist musculi dorsi function exercise based on treatment group. VAS, ODI scores and BMD before operation, 3 d, 2 weeks, 1 month, 6 months and 12 months after operation were detected and compared.</p><p><b>RESULTS</b>All operation were performed successfully,38 cases (45 vertebrae) in control group, 36 cases (44 vertebrae) in treatment group and 40 cases (49 vertebrae) were obtained complete following up, there was no significant meaning in following time among three groups (P>0.05). Postoperative VAS and ODI scores at 3 d, 2 weeks and 1 month among three groups were lower than that of before operation (P<0.01). Compared with control group, postoperative VAS score at 3 d, 2 weeks and 1 month were decreasedin treatment group and comprehensive group, but there was no significant meaning in ODI scores (P>0.05). At 6 and 12 months after operation,there was no significant differences in VAS and ODI between control group and treatment group (P>0.05), while VAS score in comprehensive group decreased much than other two groups,decreased continuously (P<0.01). At 12 months after operation, BMD among three groups were increased more than preoperative,and BMD in comprehensive group was more obviously than that of in control and treatment group.</p><p><b>CONCLUSION</b>PKP, an effective method for the treatment of thoracic and lumbar vertebral osteoporotic fracture, could improve short-term clinical effects by adding calcitonin with calcium supplements and activated vitamin D. Waist musculi dorsi function exercise could improve long-term clinical effects of PKP and improve quality of life.</p>

Synthesis and antimicrobial evaluation of pogostone and its analogues.

Pogostone (PO) is one of the secondary metabolites from Pogostemon cablin (Blanco) Benth. (Lamiaceae), serving as the effective component of the antimicrobial activity. In this study, PO and a series of its analogues were synthesized by the reaction of dehydroacetate and aldehydes in tetrahydrofuran under a nitrogen atmosphere. Their activities against Candida albicans, Gram positive bacteria and Gram negative bacteria were evaluated. The antifungal results demonstrated that PO (MIC ranged from 12 to 97µg/mL against all strains, MFC ranged from 49 to 97µg/mL against all strains) and A3 (MIC ranged from 12 to 49, MFC over 195µg/mL) showed a strong activity against Candida albicans. While A1 (MIC ranged from 49 to 97µg/mL) and A2 (MIC ranged from 24 to 49µg/mL) have only shown effect against Guangzhou clinical isolates, the antibacterial results demonstrated that PO and its analogues showed no effects against the tested bacteria strains. This study suggests that pogostone analogues, with the appropriated structure modification, represented a kind of promising antifungal agents.

Anti-Candida albicans activity and pharmacokinetics of pogostone isolated from Pogostemonis Herba.

The present work was designed to evaluate the in vitro and in vivo anti-Candida activity of pogostone (PO), a natural product isolated from Pogostemon cablin (Blanco) Benth. PO showed potent in vitro activity against clinical Candida spp. isolates tested in this study. PO and the reference drug voriconazole (VRC) were equally effective against all the fluconazole-resistant Candida albicans strains, with MIC ranging from 3.1 µg/ml to 50 µg/ml. Besides, PO was fungicidal against all Candida isolates with MFC ranging from 50 µg/ml to 400 µg/ml. By contrast, VRC was fungistatic as it failed to elicit a fungicidal effect against the Candida spp. isolates at the highest tested concentration (400 µg/ml). Furthermore, oral and topical PO administration effectively reduced the fungal load in vagina of vulvovaginal candidiasis mouse models. Topical PO administration (1.0-4.0 mg/kg) demonstrated higher activity against the vulvovaginal candidiasis than VRC (4.0 mg/kg). The pharmacokinetics and safety profile of PO were also investigated. The pharmacokinetics assay revealed that PO was easily absorbed after oral administration in mice, which might account for its in vivo anti-Candida effect. The acute toxicity test showed that the median lethal dose of PO in mice was 355 mg/kg, which was much higher than the daily dose used for the therapeutic experiments. This study demonstrated the potential of PO as a promising candidate for the treatment of Candida infections, particularly for vulvovaginal candidiasis.

Fingerprinting and simultaneous determination of alkaloids in Picrasma quassioides from different locations by high performance liquid chromatography with photodiode array detection.

A simple and sensitive method was developed and validated for profiling and simultaneous quantitation of seven alkaloids (6-hydroxy-ß-carboline-1-carboxylic acid, ß-carboline-1-carboxylic acid, ß-carboline-1-propanoic acid, 3-methylcanthin-5,6-dione, 5-hydroxy-4-methoxycanthin-6-one, 1-methoxycarbony-ß-carboline, and 4,5-dimethoxycanthin-6-one) in Picrasma quassioide grown in different locations by high-performance liquid chromatography with photodiode array detection. The analysis was conducted on a Phenomenex Gemini C(18) column at 35°C with mobile phase of 25 mM aqueous ammonium acetate (pH 4.0, adjusted by glacial acetate acid) and acetonitrile. A common fingerprint chromatograph under 254 nm consisting of 27 peaks was constructed for the evaluation of the similarities among 31 P. quassioide samples. Samples from Guangdong and Guangxi Provinces were found to be within group linkage and showed significant difference from that of Jiangxi Province origin by using principal component analysis and hierarchical clustering analysis. In addition, the seven alkaloids were identified by electrospray ionization mass spectrometry and comparing with reference standards and literature data. All of them were determined simultaneously using the established HPLC method. This rapid and effective analytical method could be employed for quality assessment of P. quassioide, as well as pharmaceutical products containing this herbal material.