Functional membrane microdomains (FMMs) that are mainly composed of scaffold proteins and polyisoprenoids play important roles in diverse cellular physiological processes in bacteria. The aim of this study was to identify the correlation between MK-7 and FMMs and then regulate the MK-7 biosynthesis through FMMs. Firstly, the relationship between FMMs and MK-7 on the cell membrane was determined by fluorescent labeling. Secondly, we demonstrated that MK-7 is a key polyisoprenoid component of FMMs by analyzing the changes in the content of MK-7 on cell membrane and the changes in the membrane order before and after destroying the integrity of FMMs. Subsequently, the subcellular localization of some key enzymes in MK-7 synthesis was explored by visual analysis, and the intracellular free pathway enzymes Fni, IspA, HepT and YuxO were localized to FMMs through FloA to achieve the compartmentalization of MK-7 synthesis pathway. Finally, a high MK-7 production strain BS3AT was successfully obtained. The production of MK-7 reached 300.3 mg/L in shake flask and 464.2 mg/L in 3 L fermenter.
Bacillus subtilis/metabolism* ; Vitamin K 2/metabolism* ; Bioreactors/microbiology* ; Membrane Microdomains/metabolism*

Humans ; Vitamins/therapeutic use* ; Iron, Dietary ; Diabetes Mellitus, Type 2 ; Nutrition Surveys ; Diet ; Vitamin A ; Vitamin K

OBJECTIVE: To explore the clinical effect of zoledronic acid combined with vitamin K2 regimen in percutaneous vertebroplasty for multi-segment osteoporotic vertebral compression fractures(OVCFs). METHODS: This study was a retrospective control study. A total of 364 patients with OVCFs who were admitted to our spinal surgery department from January 2014 to January 2017 were selected as the study subjects. According to whether zoledronic acid combined with vitamin K2 was used to treat osteoporosis after surgery, the patients were divided into control group and experimental group. Among them, 257 patients in the control group were treated with calcium carbonate and vitamin D regimen, while 107 patients in the experimental group were treated with zoledronic acid combined with vitamin K2 regimen on the basis of the control group. Visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to evaluate the clinical effect. Pre- and post-operative bone mineral density of lumbar spine and proximal femur, vertebral height ratio of responsible vertebral body and Cobb angle of vertebral body were observed by image data. Serological indicators related to bone metabolism were detected by laboratory. The complications such as fever, dizziness, osteoarthritis, muscular and soft tissue pain and adjacent vertebral re-fracture were compared between two groups. RESULTS: There was no significant difference in general data between the two groups (<0.05). There was no significant difference in VAS score between experimental group and control group before and 24 hours after operation (>0.05);VAS score in the experimental group was significantly lower than that in the control group 1 month, 3 months and 1 year after operation(<0.05). There was no significant difference in ODI between two groups before operation(>0.05), and at the 24 hours, 3 months, 1 year after operation, the experimental group was significantly lower than the control group (<0.05). There was no significant difference in the vertebral height ratio of the responsible vertebral body and the Cobb angle before operation between two groups (>0.05). The vertebral height ratio of the responsible vertebral body in experimental group was significantly higher than that in control group and Cobb angle in experimental group was significantly lower than that in control group at 3 months and 1 year after operation (<0.05). There was no significant difference in preoperative bone mineral density of lumbar spine and proximal femur between two groups (>0.05), but at 3 months and 1 year after operation, the bone mineral density of lumbar spine and proximal femur in experimental group was significantly lower than that in control group (< 0.05). There was no significant difference in preoperative bone metabolic markers such as total type I collagen amino-terminal elongation peptide, β-collagen degradation products and 25-hydroxyvitamin D between two groups (>0.05). At 1 year after operation the total type I collagen amino-terminal elongation peptide and β-collagen degradation products in experimental group was significantly lower than that in the control group (<0.05), but the 25-hydroxyvitamin D operation in experimental group was significantly higher than that in control group(<0.05). The incidence of postoperative complications such as fever, dizziness, osteoarthritis, muscle and soft tissue pain and adjacent vertebral re-fracture in experimental group was significantly lower than that in control group (<0.05). CONCLUSION Zoledronic acid injection combined with vitamin K2 regimen can be used for anti-osteoporosis treatment of OVCFs vertebroplasty. It has a definite curative effect and a high safety factor. It is worth popularizing.
Bone Cements ; Fractures, Compression ; Humans ; Kyphoplasty ; Osteoporotic Fractures ; Retrospective Studies ; Spinal Fractures ; Treatment Outcome ; Vertebroplasty ; Vitamin K 2 ; Zoledronic Acid

Several theories have been proposed to explain the etiology of adolescent idiopathic scoliosis (AIS) until present. However, limited data are available regarding the impact of vitamin D insufficiency or deficiency on scoliosis. Previous studies have shown that vitamin D deficiency and insufficiency are prevalent in adolescents, including AIS patients. A series of studies conducted in Hong Kong have shown that as many as 30% of these patients have osteopenia. The 25-hydroxyvitamin D3 level has been found to positively correlate with bone mineral density (BMD) in healthy adolescents and negatively with Cobb angle in AIS patients; therefore, vitamin D deficiency is believed to play a role in AIS pathogenesis. This study attempts to review the relevant literature on AIS etiology to examine the association of vitamin D and various current theories. Our review suggested that vitamin D deficiency is associated with several current etiological theories of AIS. We postulate that vitamin D deficiency and/or insufficiency affects AIS development by its effect on the regulation of fibrosis, postural control, and BMD. Subclinical deficiency of vitamin K2, a fat-soluble vitamin, is also prevalent in adolescents; therefore, it is possible that the high prevalence of vitamin D deficiency is related to decreased fat intake. Further studies are required to elucidate the possible role of vitamin D in the pathogenesis and clinical management of AIS.
Adolescent ; Bone Density ; Bone Diseases, Metabolic ; Calcifediol ; Fibrosis ; Hong Kong ; Humans ; Prevalence ; Scoliosis ; Vitamin D Deficiency ; Vitamin D ; Vitamin K ; Vitamin K 2 ; Vitamins

BACKGROUNDS/AIMS: Vitamin K may plays a role in controlling hepatocellular carcinoma (HCC) cell growth. In this study, we intended to present 5-year experience of 72 patients receiving oral vitamin K with or without sorafenib. Its end-point was to evaluate the safety of combination therapy using sorafenib and vitamin K. METHODS: An interim analysis was performed as a single-arm cross-sectional study, including 72 HCC patients who underwent liver resection or transplantation and administered oral vitamin K2 alone (n=47) or with sorafenib (n=25). RESULTS: In all patients, administration of vitamin K2 analog 45 mg/day did not show any noticeable adverse side-effect during vitamin K therapy of 23.3+/-10.6 months, except for one patient who experienced skin rash at the third day of vitamin K therapy. In 25 patients receiving sorafenib and vitamin K for 6 months or longer, any noticeable adverse side-effect suspected of vitamin K origin was not identified yet. A small proportion of patients showed unexpectedly favorable anti-tumor effects after use of vitamin K with or without sorafenib. CONCLUSIONS: Because add-on of oral vitamin K did not increase the adverse side-effects of sorafenib, a combination therapy with these two agents appears to be worthy of further clinical trial with an expectation of synergistic therapeutic effects.
Carcinoma, Hepatocellular* ; Cross-Sectional Studies ; Exanthema ; Humans ; Liver ; Neoplasm Metastasis ; Vitamin K 2 ; Vitamin K*

OBJECTIVES: To describe prescription patterns by gynecologists for osteoporosis therapy and to compare with the prescription patterns by physicians of other medical specialties based on the data from the Health Insurance Review and Assessment Service. METHODS: A total of 28,568 prescription claims by gynecologists of 633,870 prescription claims by physicians with medications for osteoporosis alone or medications for other indications, including osteoporosis, were analyzed. The medications for osteoporosis alone were, selective estrogen receptor modulators (SERMs), calcitonin (injection or nasal spray), vitamin K2, ipriflavone, and fluoride. The medications for other indications including osteoporosis were estrogen, tibolone, testosterone, calcium, calcium-vitamin D complex, vitamin D, and oxymetholone. RESULTS: Anti-osteoporosis medications were prescribed by 4.7% of gynecologists. Calcium and vitamin D were the most commonly prescribed medications by gynecologists (60.7%), followed by hormones, including tibolone (44%). Bisphosphonates, including bisphosphonate complex, were prescribed by 27.5% of gynecologists and SERMs were prescribed by 3.6% of gynecologists. Amongst all prescribers, the percentage of gynecologists was highest for hormones (50.6%), followed by tibolone (31.0%). When both medications were combined, the percentage of gynecologists among prescribers was 81.6%. The combination rate of calcium with other anti-osteoporosis medications was highest in gynecologists among prescribers of medical specialties (34.1%). CONCLUSION: A very small percentage of gynecologists prescribed anti-osteoporosis medications, while calcium, vitamin D, and hormones, including tibolone, were commonly prescribed by gynecologists.
Calcitonin ; Calcium ; Diphosphonates ; Estrogens ; Fluorides ; Insurance, Health ; Isoflavones ; Norpregnenes ; Osteoporosis ; Prescriptions ; Selective Estrogen Receptor Modulators ; Testosterone ; Vitamin D ; Vitamin K 2

OBJECTIVES: To describe prescription patterns by gynecologists for osteoporosis therapy and to compare with the prescription patterns by physicians of other medical specialties based on the data from the Health Insurance Review and Assessment Service. METHODS: A total of 28,568 prescription claims by gynecologists of 633,870 prescription claims by physicians with medications for osteoporosis alone or medications for other indications, including osteoporosis, were analyzed. The medications for osteoporosis alone were, selective estrogen receptor modulators (SERMs), calcitonin (injection or nasal spray), vitamin K2, ipriflavone, and fluoride. The medications for other indications including osteoporosis were estrogen, tibolone, testosterone, calcium, calcium-vitamin D complex, vitamin D, and oxymetholone. RESULTS: Anti-osteoporosis medications were prescribed by 4.7% of gynecologists. Calcium and vitamin D were the most commonly prescribed medications by gynecologists (60.7%), followed by hormones, including tibolone (44%). Bisphosphonates, including bisphosphonate complex, were prescribed by 27.5% of gynecologists and SERMs were prescribed by 3.6% of gynecologists. Amongst all prescribers, the percentage of gynecologists was highest for hormones (50.6%), followed by tibolone (31.0%). When both medications were combined, the percentage of gynecologists among prescribers was 81.6%. The combination rate of calcium with other anti-osteoporosis medications was highest in gynecologists among prescribers of medical specialties (34.1%). CONCLUSION: A very small percentage of gynecologists prescribed anti-osteoporosis medications, while calcium, vitamin D, and hormones, including tibolone, were commonly prescribed by gynecologists.
Calcitonin ; Calcium ; Diphosphonates ; Estrogens ; Fluorides ; Insurance, Health ; Isoflavones ; Norpregnenes ; Osteoporosis ; Prescriptions ; Selective Estrogen Receptor Modulators ; Testosterone ; Vitamin D ; Vitamin K 2

Vitamin K has been suggested to plays a role in bone metabolism. The objective of this study was to determine whether vitamin K2 supplementation is related to bone mineral density, bone formation markers, and bone resorption in ovariectomized (OVX) rats. Forty Sprague-Dawley female rats (body weight, 200 +/- 10 g) were divided into four groups: a sham group fed a control diet, a sham group fed a vitamin K2 supplemented diet, OVX fed a control diet, and OVX fed a vitamin K2 supplemented diet (3.5 mg vitamin K2/kg diet). All rats were fed the experimental diets for 6 weeks, and deionized water was provided ad libitum. Serum alkaline phosphatase activity (ALP), osteocalcin, and urinary deoxypyridinoline crosslink values were measured as markers of bone formation and resorption. Bone mineral density (BMD) and bone mineral content were measured in the spine and femur using PIXImus (GE Lunar Co., Madison, WI, USA). No significant differences in body weight gain, food intake, or food efficiency ratio were observed between the control and experimental groups. Serum ALP, osteocalcin, and urinary crosslink values were not significantly different between the vitamin K2 supplemented groups. No significant differences were observed for any of the variables in the sham group. Spine BMD values were significantly lower in the OVX than those in the sham groups. Spine and femur BMD per weight of vitamin K2 tended to be higher than the control diet group within the OVX group, but no significant differences were observed. In conclusion, dietary vitamin K2 supplementation may have a beneficial effect on spine and femur BMD in OVX rats. Further research is needed to understand the potential benefits of vitamin K2 on bone loss in OVX rats.
Alkaline Phosphatase ; Amino Acids ; Animals ; Body Weight ; Bone Density ; Bone Resorption ; Diet ; Eating ; Female ; Femur ; Humans ; Osteocalcin ; Osteogenesis ; Rats ; Salicylamides ; Spine ; Vitamin K ; Vitamin K 2 ; Vitamins ; Water

The study was aimed to investigate the possible mechanism of vitamin K(2) (VK(2)) on myelodysplastic syndrome (MDS) cell line MUTZ-1 in vitro. The flow cytometry was used to analyze apoptosis rate and the change of cell cycle. The expression of apoptosis-related genes bcl-2, survivin and bax were detected by reverse transcription-polymerase chain reaction (RT-PCR). The activity of caspase-3 was detected by chemiluminescence assay. The results indicated that the apoptosis peak on FCM and positive Annexin-V FITC on cell membrane showed that VK(2) induced apoptosis of MUTZ-1 cells in a dose-and-time-dependent manner, S and G(2) cell decrement, G(0)/G(1) cell arrest, VK(2) significantly down-regulated the expression of bcl-2 and survivin, but had no effect on the expression of bax, the activity of caspase-3 was significantly increased. It is concluded that VK(2) induces apoptosis of MUTZ-1 cells through activating caspase-3 pathways and the apoptosis-related genes bcl-2 and survivin may play important roles in the process of apoptosis induction.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Myelodysplastic Syndromes ; drug therapy ; pathology ; Neoplasm Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Vitamin K 2 ; pharmacology ; bcl-2-Associated X Protein ; biosynthesis ; genetics

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest.
Vitamin K 2/chemistry/metabolism/*pharmacology ; Tomography, X-Ray Computed ; Tibia/pathology ; Rats ; Osteoporosis/*drug therapy/*prevention & control ; Male ; Magnesium Deficiency/diagnosis ; Magnesium/metabolism ; Homeostasis ; Female ; *Disease Models, Animal ; Diphosphonates ; Calcium/metabolism ; Bone and Bones/*drug effects/metabolism ; Bone Resorption ; Bone Diseases, Metabolic/*metabolism ; Animals