Gut microbiota-dependent Trimethylamine N-Oxide are related with hip fracture in postmenopausal women: a matched case-control study.

The study evaluates the serum levels of Trimethylamine N-Oxide (TMAO), a gut microbial metabolite, in 286 postmenopausal women with hip fracture. From January 1, 2018 to December 31, 2018, eligible patients were included. Same women without fracture mated age were enrolled. TMAO serum levels were tested by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The serum levels of TMAO were significantly higher in patients with hip fracture than in those controls (P<0.001). The serum levels of TMAO were also higher in patients with hip fracture only than in those who also had upper limb fracture (P=0.001). High level of TMAO was proved a predictor of both hip fracture and had upper limb fracture combined hip fracture, after the adjustment of other existing risk factors [e.g., for each 1 uM increase of TMAO, odd ratio 1.16 (95% CI, 1.07-1.25), P < 0.001; and 1.12 (95% CI, 1.03-1.26), P=0.008, respectively]. In summary, increased TMAO serum levels associated with high risk of hip fracture, suggesting that increase TMAO may contribute to osteoporosis and fracture in postmenopausal women.

Low 25(OH) D serum levels are related with hip fracture in postmenopausal women: a matched case-control study.

PURPOSE: There is limited information on the prevalence of vitamin D deficiency among patients diagnosed with hip fracture in the Chinese Han population. Therefore, the aim of this study was to assess the effects of change in the serum levels of 25-hydroxyvitamin D [25(OH) D] and intact parathyroid hormone (iPTH) among postmenopausal women in North China with confirmed hip fracture. METHODS: This study was done from May 1, 2012 to April 30, 2014. Three hundred and forty-nine postmenopausal women who were diagnosed with first-ever hip fracture and 349 matched controls without fracture were used for this study. The 25(OH) D, iPTH, alkaline phosphatase, calcium, and phosphorus levels were measured in fasting venous blood samples collected from the subjects. A predesigned questionnaire was used to collect information on covariates for multivariate analyses to evaluate the hypothesized relationship between vitamin D deficiency and fracture risk. RESULTS: The serum 25(OH) D levels were found to be significantly (P < 0.0001) lower in hip fracture patients than in the controls [37.0 (interquartile range [IQR] 28.0-48.0) nmol/L vs. 41.3 (IQR 32.0-54.5) nmol/L; P < 0.0001], and the iPTH levels were significantly higher in the former group [10.2 (IQR 6.3-14.9) pmol/L vs. 5.8 (IQR 4.1-6.6) pmol/L; P < 0.0001]. Further, a 25(OH) D level ≤50 nmol/L was found to independently indicate the occurrence of hip fracture [odds ratio (OR), 3.023; 95 % confidence interval (CI) 2.154-4.298], as well as hip fracture with concomitant upper limb fracture (OR 4.473; 95 % CI 2.984-10.532). Similarly, a serum iPTH level ≥6.8 pmol/L independently indicated the development of hip fracture (OR 2.498; 95 % CI 1.764-3.942), as well as hip fracture with concomitant upper limb fracture (OR 3.254; 95 % CI 1.998-7.984). CONCLUSIONS: Vitamin D insufficiency and secondary hyperparathyroidism were found to be common problems in the sample of postmenopausal women who had experienced hip fracture. Monitoring the alterations in the serum levels of 25(OH) D and iPTH could be applied clinically as independent risk factors for hip fracture.

[Long-term regulation of arterial pressure and essential hypertension--II. Essential hypertension].

Although the mechanisms underlying the development of essential hypertension remain elusive, many observations point to the kidney as a primary actor and sodium as the main culprit (external factor) for development of hypertension. Dietary sodium has been existed for several thousands years in human being and it seems to be a civilized food habit. However, over the last few decades, experimental, observational and clinical data have continuously indicated that excess salt intake is positively associated with elevated blood pressure. It was also found that aged people is easier to be suffered from essential hypertension. By now, essential hypertension is frequently considered as a "civilized" disease, a disease of the kidney and the disease frequently occurring in the aged people. In the present mini review these features of essential hypertension are discussed in more details.

[Long-term regulation of arterial pressure and essential hypertension--I. Long-term regulation of arterial pressure].

Arterial blood pressure is regulated not by a single pressure controlling mechanism but instead by several interrelated mechanisms, each of which performs a specific function. By now, it is clear that kidney plays a dominant role in long-term regulation of arterial pressure. It is found that urine volume output markedly increases as the arterial blood pressure rises. It is the phenomenon of pressure-diuresis. Arterial blood pressure can be kept constantly by the action of pressure-diuresis when the excess accumulation of extracellular fluid in the body occurs. During this period of time kidney excretes a larger amount of urine volume. It is thus that under the conditions of the excess accumulation of extracellular fluid in the body, high level of the arterial blood pressure can only be observed as the renal function is abnormal.

[Organotypic cerebral slice culture and the course of neuronal development in it].

OBJECTIVE: To establish a method of organotypic cerebral culture. So as to pave the way for building some neurodegenerative disease models. METHODS: Organotypic cerebral cultures were prepared from prefrontal brain of neonatal SD rats. After culturing 7 to 14 days, 3 weeks, 4 weeks and 8 weeks, respectively, cerebral slices were fixed, dehydrated and sectioned in cryostat. The sections proceeded with Nissl staining and neurofilament high molecular weight (NFH) immunohistochemical staining. The difference was observed between controls and cultured slices using normal rats as controls. RESULTS: Nissl staining showed that pyramidal neurons in cultured slices were increased in volume and lightened in staining. The delaminating construction was clear from 1 to 4 weeks after culturing. In cultured slices, immunohistochemical staining showed that NFH positive pyramidal cells appeared on layer V on the tenth day and on both layers V and III after culturing 12 days. In the control group, NFH positive pyramidal cells appeared on layer V in 5-day-old rats, and appeared on both layers V and III in over 3-week-old rats. In cultured cerebral slices, the number of pyramidal neurons on layer V in M1 area was invariable from 12 days to 2 months. CONCLUSION: Orgaotypic cerebral culture can be used to study postnatal development for neocortex and build some in vitro models for neurodegenerative diseases.

[Establishment of the organotypic model of amyotrophic lateral sclerosis from the SD rats' spinal cord].

OBJECTIVE: To establish an in vitro model of amyotrophic lateral sclerosis (ALS) from the organotypic culture of SD rats' lumber spinal cord induced by the mitochondrial inhibitor,malonate sodium. METHOD: The lumber spinal cord prepared from the 6-day-old SD rats was cut into 350 microm coronarily, cultured on the Millicell-CM inserts which make the spinal cord culturing on the interface between air and fluid. First, the optimum malonate sodium dose was determined by adding different doses into the medium and counting the living motor neuron numbers by using immuno-histochemistry staining. Second, the ALS model was established as following: the cultures were divided into the malonate groups and the control groups, adding 2 mmol/L sodium malonate into the medium of the malonate groups an the 3rd day, continue culture to 12 days with this concentration; the control groups culturing without malonate. RESULTS: The organotypic characteristics are still kept till the end of the curlturing. After adding the sodium malonate, counting the number of motor neurons and interneurons on the different spinal slices in the different groups, the number of motor neuron in the cultured spinal cord was less than control (11.00+/-2.45 vs 15.29+/-1.70 per semislice at the end of the culturing, P<0.01), but the difference of the interneuron was not significant. CONCLUSION: The amyotrophic lateral sclerosis model is successful with selective injury of motor neuron, and this model can be used for the exploring of the theraptic method and its pathogenesis.

A novel PPAR alpha/gamma dual agonist inhibits cell growth and induces apoptosis in human glioblastoma T98G cells.

AIM: To examine the effect of a novel peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist TZD18 on cell proliferation and apoptosis in human glioblastoma T98G cells and its possible mechanism. METHODS: RT-PCR, MTT, TUNEL, Flow cytometry, and Western blot analysis were employed. RESULTS: TZD18 inhibited the growth of T98G cells in a concentration-dependent manner, which was associated with a G1 to S cell cycle arrest. Besides, significant apoptosis was induced after treatment with a non-toxic dose of TZD18. During the process, the expression of Bcl-2 protein was down-regulated, while that of Bax and p27kip proteins was up-regulated, and the activity of caspase-3 was elevated. However, this effect appeared to be PPARalpha and PPARgamma independent since their antagonists could not reverse this effect. CONCLUSIONS: TZD18, a novel PPARalpha/gamma dual agonist, inhibited cell growth and induce apoptosis in human glioblastoma T98G cells in vitro, indicating a therapeutic potential for TZD18 in the treatment of glioblastoma.

[Ion channels on T lymphocyte].

There is increasing evidence to show that ion channels on lymphocytes play a very important role in the regulation of immune functions. In T lymphocytes, there are three types of ion channels on cell membrane: Ca2+, K+ and Cl- channel. The influx of Ca2+ into T lymphocyte through Ca2+ channel (CRAC) may act as a second messenger to activate T lymphocyte when antigen binds to the receptor (TCR). The efflux of K+ from T lymphocyte through the K+ channel contributes to the formation of T cell membrane potential. The level of the membrane potential may affect the influx of Ca2+ into T cells. Therefore, the activation and the functions of T cell can be regulated by K+ channel indirectly. Cl- channel in T lymphocyte was found in recent years and it is probably involved in the regulation of cell volume. The recent progress on ion channels in T lymphocyte is summarized briefly in the present paper.

[Integer multiple rhythm in the spontaneous beating rhythm of cardiac myocytes and its possible mechanism].

OBJECTIVE: To introduce the characteristics of the integer multiple rhythm of cultured cardiac myocytes and to explore the cause of its generation. METHOD: Spontaneous beating rhythms of cultured cardiac myocytes were observed with photometry system and stochastic Chay model was used to simulate the experimental results. RESULT: Integer multiple rhythm was observed in the experiment. This kind of rhythm is similar to phenomena of sinus arrest. The integer multiple rhythm similar to that of the experiments was simulated in stochastic Chay model, and was demonstrated to be induced by the mechanism of autonomous stochastic resonance. CONCLUSION: The integer multiple rhythm observed in the experiment might be generated via the effect of autonomous stochastic resonance.

A protein in pig spleen similar to immune suppressive protein of stress.

AIM: To purify a protein in pig spleens, which was similar to immune suppressive protein of stress (ISPS), and characterize its properties and functions. METHODS: 1) Pig spleen was extracted in dilute hydrochloric acid. 2) The extract was ultra-filtrated for having high molecular weight proteins (Mr>30 000). 3) The filtrates were purified with FPLC affinity chromatography. 4) The elute from FPLC was used for T-lymphocyte proliferation and ELISA test. 5) Lastly, SDS-PAGE was used to determine the molecular weight and purity of the final product. RESULTS: A protein purified from pig spleen (the pig ISPS homologue) inhibited concanavalin A (Con A)-induced mouse lymphocyte proliferation. The molecular weight of this protein was about Mr 190 000. It has a stronger selectivity against T-lymphocyte line such as Jurkat cell line and mastocyte line (P8l5) and has a weaker inhibitory activity on macrophage line (U937). CONCLUSION: A protein similar to rat/mouse ISPS was found in pig spleen. This may provide an opportunity to study its roles in tumors and autoimmune diseases.

[A preliminary study on the immune suppressive protein of stress in human tonsil].

Our previous work demonstrated that under the conditions of restraint stress and under the control of central nervous system (CNS), an immune suppressive protein of stress (ISPS) was generated in peripheral lymph tissue and released into the blood stream, acting as an immune suppressor. In the present work, a protein similar to ISPS was found in human tonsil (a peripheral lymph tissue). Human tonsil was homogenized and the extract was prepared. It was found that lymphocyte proliferation was significantly suppressed by the extract. The suppression induced by the extract was partially reversed by the monoclonal antibody against ISPS (2C4). In ELISA test, the extract was able to bind to the monoclonal antibody. By immunohistochemistry, many ISPS positive cells were found in human tonsil. The ISPS positive cells were also found in human lymph nodes. Taken together, all the results demonstrate that a protein similar to ISPS may exist in human peripheral lymphoid tissue.