Burnout and depression in college students.

Research on burnout has garnered considerable attention since its inception. However, the ongoing debate persists regarding the conceptual model of burnout and its relationship with depression. Thus, we conducted a network analysis to determine the dimensional structure of burnout and the burnout-depression overlap. The Maslach Burnout Inventory-Student Survey and Patient Health Questionnaire-9 were used to measure burnout and depression among 1096 college students. We constructed networks for burnout, depression, and a burnout-depression co-occurrence network. The results showed that cynicism symptom was the most central to the burnout network. In the co-occurrence network, depressive symptoms ("anhedonia", "fatigue") and burnout symptom ("doubting the significance of studies") were the most significant in causing burnout-depression comorbidity. Community detection revealed three communities within burnout symptoms, aligning closely with their three dimensions identified through factor analysis. Additionally, there was no overlap between burnout and depression. In conclusion, our findings support a multidimensional structure of burnout, affirming it as a distinct concept separate from depression. Cynicism, rather than exhaustion, plays the most important role in burnout and the burnout-depression comorbidity.

Oxygen enrichment protects against intestinal damage and gut microbiota disturbance in rats exposed to acute high-altitude hypoxia.

Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague-Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae_NK3B31_group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia.

Electromagnetic fields ameliorate hepatic lipid accumulation and oxidative stress: potential role of CaMKKß/AMPK/SREBP-1c and Nrf2 pathways.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is related to disturbed lipid metabolism and redox homeostasis. However, a definitive drug treatment has not been approved for this disease. Studies have found that electromagnetic fields (EMF) can ameliorate hepatic steatosis and oxidative stress. Nevertheless, the mechanism remains unclear. METHODS: NAFLD models were established by feeding mice a high-fat diet. Simultaneously, EMF exposure is performed. The effects of the EMF on hepatic lipid deposition and oxidative stress were investigated. Additionally, the AMPK and Nrf2 pathways were analysed to confirm whether they were activated by the EMF. RESULTS: Exposure to EMF decreased the body weight, liver weight and serum triglyceride (TG) levels and restrained the excessive hepatic lipid accumulation caused by feeding the HFD. The EMF boosted CaMKKß protein expression, activated AMPK phosphorylation and suppressed mature SREBP-1c protein expression. Meanwhile, the activity of GSH-Px was enhanced following an increase in nuclear Nrf2 protein expression by PEMF. However, no change was observed in the activities of SOD and CAT. Consequently, EMF reduced hepatic reactive oxygen species (ROS) and MDA levels, which means that EMF relieved liver damage caused by oxidative stress in HFD-fed mice. CONCLUSIONS: EMF may activate the CaMKKß/AMPK/SREBP-1c and Nrf2 pathways to control hepatic lipid deposition and oxidative stress. This investigation indicates that EMF may be a novel therapeutic method for NAFLD.

Keratin 18 Depletion as a Possible Mechanism for the Induction of Apoptosis and Ferroptosis in the Rat Hippocampus After Hypobaric Hypoxia.

Memory impairment is one of the neuropsychological effects of hypobaric hypoxia (HH), which can be associated with programmed cell death, such as apoptosis and ferroptosis. Emerging evidence indicates crosstalk between apoptosis and ferroptosis, while the crosstalk between HH-induced apoptosis and ferroptosis in the hippocampus has not been clarified. Here, microarray profiles were extracted to analyze the differentially expressed genes with and without HH exposure, and keratin 18 (Krt18) was found to be a potential gene related to both apoptosis and ferroptosis. Then, we conducted morphological observations that showed that apoptosis and ferroptosis coexisted in the rat hippocampus after HH exposure. Combined with the real-time q-PCR analysis, the mRNA expression of Krt18 decreased significantly after HH exposure for 1 day and 3 days, and Mapk10 (JNK3) was upregulated at the corresponding time points. After exposure for 7 days, Krt18 and JNK3 showed no significant change. In conclusion, Krt18 may regulate apoptosis and ferroptosis simultaneously, possibly via the JNK signaling pathway, which might provide a potential central target for apoptosis and ferroptosis in hippocampal injury after HH exposure.

Mental fatigue decreases complexity: Evidence from multiscale entropy analysis of instantaneous frequency variation in alpha rhythm.

Mental fatigue (MF) jeopardizes performance and safety through a variety of cognitive impairments and according to the complexity loss theory, should represent "complexity loss" in electroencephalogram (EEG). However, the studies are few and inconsistent concerning the relationship between MF and loss of complexity, probably because of the susceptibility of brain waves to noise. In this study, MF was induced in thirteen male college students by a simulated flight task. Before and at the end of the task, spontaneous EEG and auditory steady-state response (ASSR) were recorded and instantaneous frequency variation (IFV) in alpha rhythm was extracted and analyzed by multiscale entropy (MSE) analysis. The results show that there were significant differences in IFV in alpha rhythm either from spontaneous EEG or from ASSR for all subjects. Therefore, the proposed method can be effective in revealing the complexity loss caused by MF in spontaneous EEG and ASSR, which may serve as a promising analyzing method to mark mild mental impairments.

Oxygen Enrichment Mitigates High-Altitude Hypoxia-Induced Hippocampal Neurodegeneration and Memory Dysfunction Associated with Attenuated Tau Phosphorylation.

Cai, Jing, Junyong Ruan, Xi Shao, Yuanjun Ding, Kangning Xie, Chi Tang, Zedong Yan, Erping Luo, and Da Jing. Oxygen enrichment mitigates high-altitude hypoxia-induced hippocampal neurodegeneration and memory dysfunction associated with attenuated tau phosphorylation. High Alt Med Biol. 22:274-284, 2021. Background: Brain is predominantly vulnerable to high-altitude hypoxia (HAH), resulting in neurodegeneration and cognitive impairment. The technology of oxygen enrichment has proven effective to decrease the heart rate and improve the arterial oxygen saturation by reducing the equivalent altitude. However, the efficacy of oxygen enrichment on HAH-induced cognitive impairments remains controversial based on the results of neuropsychological tests, and its role in HAH-induced hippocampal morphological and molecular changes remains unknown. Therefore, this study aims to systematically investigate the effects of oxygen enrichment on the memory dysfunction and hippocampal neurodegeneration caused by HAH. Materials and Methods: Fifty-one male Sprague-Dawley rats were equally assigned to three groups: normal control, HAH, and HAH with oxygen enrichment (HAHO). Rats in the HAH and HAHO groups were exposed to hypoxia for 3 days in a hypobaric hypoxia chamber at a simulated altitude of 6,000 m. Rats in the HAHO group were supplemented with oxygen-enriched air, with 12 hours/day in the hypobaric hypoxia chamber. Results: Our results showed that oxygen enrichment improved the locomotor activity of HAH-exposed rats. The Morris water maze test revealed that oxygen enrichment significantly ameliorated HAH-induced spatial memory deficits. Oxygen enrichment also improved morphological alterations of pyramidal cells and the ultrastructure of neurons in the hippocampal CA1 region in rats exposed to acute HAH. Tau hyperphosphorylation at Ser396, Ser262, Thr231, and Thr181 was also significantly attenuated by oxygen enrichment in HAH-exposed rats. Conclusions: Together, our study reveals that oxygen enrichment can ameliorate HAH-induced cognitive impairments associated with improved hippocampal morphology and molecular expression, and highlights that oxygen enrichment may become a promising alternative treatment against neurodegeneration for humans ascending to the plateau.

Spatiotemporal characterization of microdamage accumulation and its targeted remodeling mechanisms in diabetic fatigued bone.

The skeleton of type 1 diabetes mellitus (T1DM) has deteriorated mechanical integrity and increased fragility, whereas the mechanisms are not fully understood. Load-induced microdamage naturally occurs in bone matrix and can be removed by initiating endogenous targeted bone remodeling. However, the microdamage accumulation in diabetic skeleton and the corresponding bone remodeling mechanisms remain poorly understood. Herein, streptozotocin-induced T1DM rats and age-matched non-diabetic rats were subjected to daily uniaxial ulnar loading for 1, 4, 7, and 10 days, respectively. The SPECT/CT and basic fuchsin staining revealed significant higher-density spatial accumulation of linear and diffuse microdamage in diabetic ulnae than non-diabetic ulnae. Linear microcracks increased within 10-day loading in diabetic bone, whereas peaked at Day 7 in non-diabetic bone. Moreover, diabetic fatigued ulnae had more severe disruptions of osteocyte canaliculi around linear microcracks. Immunostaining results revealed that diabetes impaired targeted remodeling in fatigued bone at every key stage, including increased apoptosis of bystander osteocytes, decreased RANKL secretion, reduced osteoclast recruitment and bone resorption, and impaired osteoblast-mediated bone formation. This study characterizes microdamage accumulation and abnormal remodeling mechanisms in the diabetic skeleton, which advances our etiologic understanding of diabetic bone deterioration and increased fragility from the aspect of microdamage accumulation and bone remodeling.

Oxygen Enrichment Ameliorates Cardiorespiratory Alterations Induced by Chronic High-Altitude Hypoxia in Rats.

Chronic high-altitude hypoxia (HAH) results in compensatory pathological adaptations, especially in the cardiorespiratory system. The oxygen enrichment technology can provide long-lasting oxygen supply and minimize oxygen toxicity, which has proven to be effective to increase oxygen saturation, decrease heart rate, and improve human exercise performance after ascending to high altitudes. Nevertheless, it remains unknown whether oxygen enrichment can resist chronic HAH-induced cardiorespiratory alterations. Thirty-six male rats were equally assigned to the normal control (NC), HAH, and HAH with oxygen enrichment (HAHO) groups. The HAH and HAHO rats were housed in a hypobaric hypoxia chamber equivalent to 5,000 m for 4 weeks. The HAHO rats were exposed to oxygen-enriched air for 8 h/day. We found that oxygen enrichment mitigated the augmented skin blood flow and improved the locomotor activity of HAH-exposed rats. Oxygen enrichment inhibited HAH-induced increase in the production of red blood cells (RBCs). The hemodynamic results showed that oxygen enrichment decreased right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) in HAH-exposed rats. HAH-associated right ventricular hypertrophy and cardiomyocyte enlargement were ameliorated by oxygen enrichment. Oxygen enrichment inhibited HAH-induced excessive expression of cytokines associated with cardiac hypertrophy and myocardial fibrosis [angiotensin-converting enzyme (ACE)/angiotensin-converting enzyme 2 (ACE2), angiotensin II (Ang II), collagen type I alpha 1 (Col1α1), collagen type III alpha 1 (Col3α1), and hydroxyproline] in the right ventricle (RV). Oxygen enrichment inhibited medial thickening, stenosis and fibrosis of pulmonary arterioles, and cytokine expression related with fibrosis (Col1α1, Col3α1, and hydroxyproline) and pulmonary vasoconstriction [endothelin-1(ET-1)] in HAH-exposed rats. This study represents the first effort testing the efficacy of the oxygen enrichment technique on cardiopulmonary structure and function in chronic HAH animals, and we found oxygen enrichment has the capability of ameliorating chronic HAH-induced cardiopulmonary alterations.

Spatiotemporal Distribution of Linear Microcracks and Diffuse Microdamage Following Daily Bouts of Fatigue Loading of Rat Ulnae.

Microdamage accumulation contributes to impaired skeletal mechanical integrity. The bone can remove microdamage by initiating targeted bone remodeling. However, the spatiotemporal characteristics of microdamage initiation and propagation and their relationship with bone remodeling in response to fatigue loading, especially for more physiologically relevant daily bouts of compressive loading, remain poorly understood. The right forelimbs of 24 rats were cyclically loaded with a ramp waveform for 1,500 cycles/day, and contralateral ulnae were not loaded as the controls. The rats were divided into four equal groups and loaded for 1, 4, 7, and 10 days, respectively. We demonstrated that linear microcracking accumulation exhibited a non-linear time-varying process within 10 days of loading with peaked microcrack density at Day 7. Disrupted canaliculi surrounding linear microcracks showed high similarity with the temporal changes of linear microcracking accumulation. Observable intracortical resorption regions were found on Day 10. We found more linear microcracks accumulated in the tensile cortex, but longer cracks were observed in the compressive sides. Increased accumulation of diffuse microdamage was observed from Day 4, but no obvious peak was observed within the 10-day loading period. Diffuse damage first initiated in the compressive cortices but extended to tension from Day 7. The diffuse damage exhibited no impacts on the surrounding osteocyte integrity. Together, our findings revealed a time-dependent, bone remodeling-mediated varying process of linear microcracking accumulation following daily bouts of fatigue loading (with observable peak at Day 7 under our loading regime). Our study also identified distinct spatial accumulation of linear and diffuse microdamage in rat ulnae with tensile and compressive strains. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2112-2121, 2019.

Pulsed electromagnetic fields (PEMF) attenuate changes in vertebral bone mass, architecture and strength in ovariectomized mice.

Pulsed electromagnetic fields (PEMF) has been investigated as a noninvasive alternative method to prevent bone loss for postmenopausal osteoporosis (OP), and the bone tissue involved in these studies are usually long bones such as femur and tibia in OP patients or rat models. However, few studies have investigated the effects of PEMF on the vertebral bone in mice with OP. This study aimed to investigate whether PEMF preserve lumbar vertebral bone mass, microarchitecture and strength in ovariectomized (OVX) mouse model of OP and its associated mechanisms. Thirty 3-month-old female BALB/c mice were randomly divided into three groups (n=10): sham-operated control (Sham), ovariectomy (OVX), and ovariectomy with PEMF treatment (OVX+PEMF). The OVX+PEMF group was exposed to 15Hz, 1.6 mT PEMF for 8h/day, 7days/week. After 8weeks, the mice were sacrificed. The OVX+PEMF group showed lower body weight gain of mice induced by estrogen deficiency compared with OVX group. Biochemical analysis of serum demonstrated that serum bone formation markers including bone specific alkaline phosphatase (BALP), serum osteocalcin (OCN), osteoprotegerin (OPG) and N-terminal propeptide of type I procollagen (P1NP) were markedly higher in OVX+PEMF group compared with OVX group. Besides, serum bone resorption markers including tartrate-resistant acid phosphatase 5b (TRAP-5b) and C-terminal crosslinked telopeptides of type I collagen (CTX-I) were markedly lower in OVX+PEMF group compared with OVX group. Biomechanical test observed that OVX+PEMF group showed higher compressive maximum load and stiffness of the lumbar vertebrae compared with OVX group. Micro-computed tomography (µCT) and histological analysis of lumbar vertebrae revealed that PEMF partially prevented OVX-induced decrease of trabecular bone mass and deterioration of trabecular bone microarchitecture in lumbar vertebrae. Real-time PCR showed that the canonical Wnt signaling pathway of the lumbar vertebrae, including Wnt3a, LRP5 and ß-catenin were markedly up-regulated in OVX+PEMF group compared with OVX group. Moreover, the mRNA expressions of RANKL and OPG were markedly up-regulated in OVX+PEMF group compared with OVX group, whereas no statistical difference in RANKL/OPG mRNA ratio was found between OVX+PEMF group and OVX group. Besides, our study also found that the RANK mRNA expression was down-regulated in OVX+PEMF group compared with OVX group. Taken together, we reported that long-term stimulation with PEMF treatment was able to alleviate lumbar vertebral OP in postmenopausal mice through a combination of increased bone formation and suppressed bone resorption related to regulating the skeletal gene expressions of Wnt3a/LRP5/ß-catenin and OPG/RANKL/RANK signaling pathways.

Effects of four kinds of electromagnetic fields (EMF) with different frequency spectrum bands on ovariectomized osteoporosis in mice.

Electromagnetic fields (EMF) was considered as a non-invasive modality for treatment of osteoporosis while the effects were diverse with EMF parameters in time domain. In present study, we extended analysis of EMF characteristics from time domain to frequency domain, aiming to investigate effects of four kinds of EMF (LP (1-100 Hz), BP (100-3,000 Hz), HP (3,000-50,000 Hz) and AP (1-50,000 Hz)) on ovariectomized (OVX) osteoporosis (OP) in mice. Forty-eight 3-month-old female BALB/c mice were equally assigned to Sham, OVX, OVX + LP, OVX + BP, OVX + HP and OVX + AP groups (n = 8). After 8-week exposure (3 h/day), LP and BP significantly increased serum bone formation markers and osteogenesis-related gene expressions compared with OVX. Bedsides, LP and BP also slightly increased bone resorption activity compared with OVX, evidenced by increased RANKL/OPG ratio. HP sharply decreased serum bone formation and resporption markers and osteogenesis and osteoclastogenesis related gene expressions compared with OVX. AP had accumulative effects of LP, BP and HP, which significantly increased bone formation and decreased bone resporption activity compared with OVX. As a result, LP, BP and HP exposure did not later deterioration of bone mass, microarchitecture and mechanical strength in OVX mice with OP. However, AP stimulation attenuated OVX-induced bone loss.

Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/ß-catenin signaling-associated mechanism.

Treatment of osseous defects remains a formidable clinical challenge. Porous titanium alloys (pTi) have been emerging as ideal endosseous implants due to the excellent biocompatibility and structural properties, whereas inadequate osseointegration poses risks for unreliable long-term implant stability. Substantial evidence indicates that pulsed electromagnetic fields (PEMF), as a safe noninvasive method, inhibit osteopenia/osteoporosis experimentally and clinically. We herein investigated the efficiency and potential mechanisms of PEMF on osteogenesis and osseointegration of pTi in vitro and in vivo. We demonstrate that PEMF enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton for in vitro osteoblasts seeded in pTi. PEMF promoted gene expressions in Runx2, OSX, COL-1 and Wnt/ß-catenin signaling. PEMF-stimulated group exhibited higher Runx2, Wnt1, Lrp6 and ß-catenin protein expressions. In vivo results via µCT and histomorphometry show that 6-week and 12-week PEMF promoted osteogenesis, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defect. PEMF promoted femoral gene expressions of Runx2, BMP2, OCN and Wnt/ß-catenin signaling. Together, we demonstrate that PEMF improve osteogenesis and osseointegration of pTi by promoting skeletal anabolic activities through a Wnt/ß-catenin signaling-associated mechanism. PEMF might become a promising biophysical modality for enhancing the repair efficiency and quality of pTi in bone defect.

Effects of extremely low frequency pulsed magnetic fields on diabetic nephropathy in streptozotocin-treated rats.

BACKGROUND: Extremely low frequency pulsed magnetic fields (ELFPMF) have been shown to induce Faraday currents and measurable effects on biological systems. A kind of very high frequency electromagnetic field was reported that it improved the symptoms of diabetic nephropathy (DN) which is a major complication of diabetes. However, few studies have examined the effects of ELFPMF DN at the present. The present study was designed to investigate the effects of ELFPMF on DN in streptozotocin (STZ)-induced type 1 diabetic rats. METHODS: Adult male SD rats were randomly divided into three weight-matched groups: Control (non-diabetic rats without DN), DN + ELFPMF (diabetic rats with DN exposed to ELFPMF, 8 h/days, 6 weeks) and DN (diabetic rats with DN exposed to sham ELFPMF). Renal morphology was examined by light and electron microscopy, vascular endothelial growth factor (VEGF)-A and connective tissue growth factor (CTGF) were measured by enzyme linked immune sorbent assay. RESULTS: After 6 weeks' ELFPMF exposure, alterations of hyperglycemia and weight loss in STZ-treated rats with DN were not found, while both positive and negative effects of ELFPMF on the development of DN in diabetic rats were observed. The positive one was that ELFPMF exposure attenuated the pathological alterations in renal structure observed in STZ-treated rats with DN, which were demonstrated by slighter glomerular and tubule-interstitial lesions examined by light microscopy and slighter damage to glomerular basement membrane and podocyte foot processes examined by electron microscopy. And then, the negative one was that ELFPMF stimulation statistically significantly decreased renal expression of VEGF-A and statistically significantly increased renal expression of CTGF in diabetic rats with DN, which might partially aggravate the symptoms of DN. CONCLUSION: Both positive and negative effects of ELFPMF on the development of DN in diabetic rats were observed. The positive effect induced by ELFPMF might play a dominant role in the procession of DN in diabetic rats, and it is suggested that the positive effect should be derived from the correction of pathogenic diabetes-induced mediators.

Decreased neuronal bursting and phase synchrony in the hippocampus of streptozotocin diabetic rats.

Diabetic encephalopathy is one of the complications of diabetes. Cognitive dysfunction is the main consequence. Previous findings from neuroanatomical and in vitro electrophysiological studies showed that the structure and function of the hippocampus is impaired in diabetes, which may underlie the cognitive dysfunction induced by diabetes. However the study of electrophysiological abnormality of hippocampal neurons in intact networks is sparse. In the current study, we recorded the spontaneous firing of neurons in hippocampal CA1 area in anesthetized streptozotozin (STZ)-diabetic and age-matched control rats. Profound reduction in burst activity was found in diabetic rats. Compared to control rats, the intra-burst inter-spike intervals were prolonged significantly in diabetic rats, while the burst ratio and the mean number of spikes within a burst decreased significantly. Treatment with APP 17-mer peptide retarded the effects of diabetes on these parameters. In addition, the average PLV of diabetic rats was lower than that of control rats. These findings provide in vivo electrophysiological evidence for the impairment of hippocampal function in STZ-diabetic rats, and may have some implications in the mechanisms associated with cognitive deficits in diabetes.

Moderate-intensity rotating magnetic fields do not affect bone quality and bone remodeling in hindlimb suspended rats.

Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF), another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates potentially obvious waveform-dependent effects of electromagnetic fields-stimulated osteogenesis, suggesting that RMF, at least in the present form, might not be an optimal modality for inhibiting disuse osteopenia/osteoporosis.

Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.

A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, ß-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities, and imply that PEMF might become a potential biophysical treatment modality for disuse osteoporosis.

Pulsed electromagnetic fields improve bone microstructure and strength in ovariectomized rats through a Wnt/Lrp5/ß-catenin signaling-associated mechanism.

Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and ß-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/ß-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis.

An oxygen enrichment device for lowlanders ascending to high altitude.

BACKGROUND: When ascending to the high altitude, people living in low altitude areas will suffer from acute mountain sickness. The aim of this study is to test the hypothesis that whether an oxygen concentration membrane can be made and used to construct a new portable oxygen enrichment device for individuals in acute exposure to the high altitude. METHODS: The membrane was fabricated using vinylsiloxane rubber, polyphenylene oxide hydrogen silicone polymers, chloroplatinic acid and isopropyl alcohol. The membrane was assembled in a frame and the performance was tested in terms of concentration of oxygen, flow rate of oxygen enriched air, pressure ratio across the membrane and ambient temperature. Furthermore, the oxygen concentration device was constructed using the membrane, a DC fan, vacuum pump and gas buffer. A nonrandomized preliminary field test was conducted, in which eight healthy male subjects were flown to Tibet (Lhasa, 3,700 m). First, subjects wore the oxygen enrichment device and performed an incremental exercise on cycle ergometer. The test included heart rate (HR), saturation of peripheral oxygen (SpO2) and physical work capacity (PWC). Then, after a rest period of 4 hours, the experimental protocol was repeated without oxygen enrichment device. RESULTS: The testing showed that the membrane could increase the oxygen concentration by up to 30%. Simulation test indicated that although the performance of the oxygen enrichment device decreased with altitudes, the oxygen concentration could still maintain 28% with flow rate of enriched air 110 cm3/s at 5000 m. The field test showed that higher SpO2, lower HR, and better PWC (measured by the PWC-170) were observed from all the subjects using oxygen enrichment device compared with non-using (P < 0.01). CONCLUSIONS: We concluded that the new portable oxygen enrichment device would be effective in improving exercise performance when ascending to the high altitude.

Screening of osteoprotegerin-related feature genes in osteoporosis and functional analysis with DNA microarray.

BACKGROUND: Osteoporosis affects 200 million people worldwide and places an enormous economic burden on society. We aim to identify the feature genes that are related to osteoprotegerin in osteoporosis and to perform function analysis with DNA microarray from human bone marrow. METHODS: We downloaded the gene expression profile GSE35957 from Gene Expression Omnibus database including nine gene chips from bone marrow mesenchymal stem cells of five osteoporotic and four non-osteoporotic subjects. The differentially expressed genes between normal and disease samples were identified by LIMMA package in R language. The interactions among the osteoprotegerin gene (OPG) and differentially expressed genes were searched and visualized by Cytoscape. MCODE and Bingo were used to perform module analysis. Finally, GENECODIS was used to obtain enriched pathways of genes in an interaction network. RESULTS: A total of 656 genes were identified as differentially expressed genes between osteoporotic and non-osteoporotic samples. IL17RC, COL1A1, and ESR1 were identified to interact with OPG directly from the protein-protein interaction network. A module containing ERS1 was screened out, and this module was most significantly enriched in organ development. Pathway enrichment analysis suggested genes in the interaction network were related to focal adhesion. CONCLUSIONS: The expression pattern of IL17RC, COL1A1, and ESR1 can be useful in osteoporosis detection, which may help in identifying those populations at high risk for osteoporosis, and in directing treatment of osteoporosis.

Therapeutic effects of 15 Hz pulsed electromagnetic field on diabetic peripheral neuropathy in streptozotocin-treated rats.

Although numerous clinical studies have reported that pulsed electromagnetic fields (PEMF) have a neuroprotective role in patients with diabetic peripheral neuropathy (DPN), the application of PEMF for clinic is still controversial. The present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague-Dawley rats were randomly divided into three weight-matched groups (eight in each group): the non-diabetic control group (Control), diabetes mellitus with 15 Hz PEMF exposure group (DM+PEMF) which were subjected to daily 8-h PEMF exposure for 7 weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. Meanwhile, ultrastructural examination and immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. During a 7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN. However, PEMF stimulation attenuated the development of the abnormalities observed in STZ-treated rats with DPN, which were demonstrated by increased hind paw withdrawal threshold to mechanical and thermal stimuli, slighter demyelination and axon enlargement and less VEGF immunostaining of sciatic nerve compared to those of the DM group. The current study demonstrates that treatment with PEMF might prevent the development of abnormalities observed in animal models for DPN. It is suggested that PEMF might have direct corrective effects on injured nerves and would be a potentially promising non-invasive therapeutic tool for the treatment of DPN.