Selenium in plants: A nexus of growth, antioxidants, and phytohormones.

Selenium (Se) is an essential micronutrient for both human and animals. Plants serve as the primary source of Se in the food chain. Se concentration and availability in plants is influenced by soil properties and environmental conditions. Optimal Se levels promote plant growth and enhance stress tolerance, while excessive Se concentration can result in toxicity. Se enhances plants ROS scavenging ability by promoting antioxidant compound synthesis. The ability of Se to maintain redox balance depends upon ROS compounds, stress conditions and Se application rate. Furthermore, Se-dependent antioxidant compound synthesis is critically reliant on plant macro and micro nutritional status. As these nutrients are fundamental for different co-factors and amino acid synthesis. Additionally, phytohormones also interact with Se to promote plant growth. Hence, utilization of phytohormones and modified crop nutrition can improve Se-dependent crop growth and plant stress tolerance. This review aims to explore the assimilation of Se into plant proteins, its intricate effect on plant redox status, and the specific interactions between Se and phytohormones. Furthermore, we highlight the proposed physiological and genetic mechanisms underlying Se-mediated phytohormone-dependent plant growth modulation and identified research opportunities that could contribute to sustainable agricultural production in the future.

Dancers with non-specific low back pain have less lumbar movement smoothness than healthy dancers.

BACKGROUND: Ballet is a highly technical and physically demanding dance form involving extensive end-range lumbar movements and emphasizing movement smoothness and gracefulness. A high prevalence of non-specific low back pain (LBP) is found in ballet dancers, which may lead to poor controlled movement and possible pain occurrence and reoccurrence. The power spectral entropy of time-series acceleration is a useful indicator of random uncertainty information, and a lower value indicates a greater smoothness or regularity. The current study thus applied a power spectral entropy method to analyze the movement smoothness in lumbar flexion and extension in healthy dancers and dancers with LBP, respectively. METHOD: A total of 40 female ballet dancers (23 in the LBP group and 17 in the control group) were recruited in the study. Repetitive end-range lumbar flexion and extension tasks were performed and the kinematic data were collected using a motion capture system. The power spectral entropy of the time-series acceleration of the lumbar movements was calculated in the anterior-posterior (AP), medial-lateral (ML), vertical (VT), and three-directional (3D) vectors. The entropy data were then used to conduct receiver operating characteristic curve analyses to evaluate the overall distinguishing performance and thus cutoff value, sensitivity, specificity, and area under the curve (AUC) were calculated. RESULTS: The power spectral entropy was significantly higher in the LBP group than the control group in the 3D vector in both lumbar flexion and lumber extension (flexion: p = 0.005; extension: p < 0.001). In lumbar extension, the AUC in the 3D vector was 0.807. In other words, the entropy provides an 80.7% probability of distinguishing between the two groups (i.e., LBP and control) correctly. The optimal cutoff entropy value was 0.5806 and yielded a sensitivity of 75% and specificity of 73.3%. In lumbar flexion, the AUC in the 3D vector was 0.777, and hence the entropy provided a probability of 77.7% of distinguishing between the two groups correctly. The optimal cutoff value was 0.5649 and yielded a sensitivity of 90% and a specificity of 73.3%. CONCLUSIONS: The LBP group showed significantly lower lumbar movement smoothness than the control group. The lumbar movement smoothness in the 3D vector had a high AUC and thus provided a high differentiating capacity between the two groups. It may therefore be potentially applied in clinical contexts to screen dancers with a high risk of LBP.

High-efficiency decomposition of eggshell membrane by a keratinase from Meiothermus taiwanensis.

Eggshell membrane (ESM), a plentiful biological waste, consists of collagen-like proteins and glycosaminoglycans (GAGs) such as hyaluronic acid (HA). Here we used a keratinase (oeMtaker)-mediated system to decompose ESM. The best reaction condition was established by incubating the solution containing oeMtaker, sodium sulfite, and ESM with a weight ratio of 1:120:600. ESM enzymatic hydrolysate (ESM-EH) showed a high proportion of essential amino acids and type X collagen peptides with 963-2259 Da molecular weights. The amounts of GAGs and sulfated GAGs in ESM-EH were quantified as 6.4% and 0.7%, respectively. The precipitated polysaccharides with an average molecular weight of 1300-1700 kDa showed an immunomodulatory activity by stimulating pro-inflammatory cytokines (IL-6 and TNF-α) production. In addition, a microorganism-based system was established to hydrolyze ESM by Meiothermus taiwanensis WR-220. The amounts of GAGs and sulfated GAGs in the system were quantified as 0.9% and 0.1%, respectively. Based on our pre-pilot tests, the system shows great promise in developing into a low-cost and high-performance process. These results indicate that the keratinase-mediated system could hydrolyze ESM more efficiently and produce more bioactive substances than ever for therapeutical applications and dietary supplements.

Anti-Inflammatory CDGSH Iron-Sulfur Domain 2: A Biomarker of Central Nervous System Insult in Cellular, Animal Models and Patients.

Spinal cord injury (SCI) promotes brain inflammation; conversely, brain injury promotes spinal neuron loss. There is a need to identify molecular biomarkers and therapeutic targets for central nervous system (CNS) injury. CDGSH iron-sulfur structural domain 2 (CISD2), an NF-κB antagonist, is downregulated after injury in vivo and in vitro. We aimed to examine the diagnostic value of CISD2 in patients with CNS insult. Plasma and cerebrospinal fluid (CSF) CISD2 levels were decreased in 13 patients with CNS insult and were negatively correlated with plasma IL6 levels (associated with disease severity; r = −0.7062; p < 0.01). SCI-induced inflammatory mediators delivered through CSF promoted mouse brain inflammation at 1 h post-SCI. Anti-CISD2 antibody treatment exacerbated SCI-induced inflammation in mouse spine and brain. Lipopolysaccharide-stimulated siCISD2-transfected EOC microglial cells exhibited proinflammatory phenotypes (enhanced M1 polarization, decreased M2 polarization, and increased intranuclear NF-κB p65 translocation). Plasma and CSF CISD2 levels were increased in three patients with CNS insult post-therapeutic hypothermia. CISD2 levels were negatively correlated with plasma and CSF levels of inflammatory mediators. CISD2 inhibition and potentiation experiments in cells, animals, and humans revealed CISD2 as a biomarker for CNS insult and upregulation of CISD2 anti-inflammatory properties as a potential therapeutic strategy for CNS insult.

Freshwater Clam Extract Mitigates Neuroinflammation and Amplifies Neurotrophic Activity of Glia: Insights from In Vitro Model of Neurodegenerative Pathomechanism.

BACKGROUND: An extensive body of research suggests that brain inflammation and oxidative stress are the underlying causes of Parkinson's disease (PD), for which no potent therapeutic approach exists to mitigate the degradation of dopamine neurons. Freshwater clams, an ancient health food of Chinese origin, have been documented to exhibit anti-inflammatory and antioxidant effects. We previously reported that freshwater clam extract (FCE) can attenuate astrocytic activation and subsequent proinflammatory cytokine production from substantia nigra in an MPTP-induced PD mouse model. This article provides insight into the potential mechanisms through which FCE regulates neuroinflammation in a glia model of injury. MATERIALS AND METHODS: In total, 1 µg/mL lipopolysaccharide (LPS) and 200 µM rotenone were conducted in primary glial cell cultures to mimic the respective neuroinflammation and oxidative stress during injury-induced glial cell reactivation, which is relevant to the pathological process of PD. RESULTS: FCE markedly reduced LPS-induced neuroinflammation by suppressing NO and TNF-α production and the expression of pro-inflammatory cytokines. In addition, FCE was effective at reducing rotenone-induced toxicity by diminishing ROS production, promoting antioxidant enzymes (SOD, catalase, and GPx) and minimizing the decline in glial-cell-secreted neurotrophic factors (GDNF, BDNF). These impacts ultimately led to a decrease in glial apoptosis. CONCLUSIONS: Evidence reveals that FCE is capable of stabilizing reactive glia, as demonstrated by reduced neuroinflammation, oxidative stress, the increased release of neurotrophic factors and the inhibition of apoptosis, which provides therapeutic insight into neurodegenerative diseases, including PD.

Effect of Integrated Training on Balance and Ankle Reposition Sense in Ballet Dancers.

OBJECTIVE: To investigate the effects of a 6-week integrated training program on the ankle joint reposition sense and postural stability in ballet dancers. METHODS: Sixteen female ballet dancers participated in the study and underwent a 6-week integrated training program consisting of plyometric, proprioception and core stability exercises along with a home program involving additional ankle muscle strengthening and stretching. The ankle joint reposition tests and the parameters of the center of pressure (COP) while performing grand-plie (deep squatting) and releve en demi-pointe (standing on balls of foot) movements were measured before and after training. RESULTS: After 6 weeks, participants showed significantly smaller absolute ankle joint reposition errors in dorsiflexion (p = 0.031), plantarflexion (p = 0.003) and eversion (p = 0.019) compared to the pre-training measurement. Furthermore, after training, a significantly slower average COP speed at pre-equilibrium during grand-plie movement (p = 0.003) and pre-equilibrium phase of releve en demi-pointe (p = 0.023) were observed. In addition, the maximum COP displacement in the medial-lateral direction was significantly smaller at pre-equilibrium phase during grand-plie (p = 0.044) and releve en demi-pointe movements (p = 0.004) after training. CONCLUSIONS: The 6-week integrated training program improved the ankle joint reposition sense and postural control in the medial-lateral direction during grand-plie and releve en demi-pointe movements.

Ultrarapid Inflammation of the Olfactory Bulb After Spinal Cord Injury: Protective Effects of the Granulocyte Colony-Stimulating Factor on Early Neurodegeneration in the Brain.

The correlation among olfactory dysfunction, spinal cord injury (SCI), subjective cognitive decline, and neurodegenerative dementia has been established. Impaired olfaction is considered a marker for neurodegeneration. Hence, there is a need to examine if SCI leads to olfactory dysfunction. In this study, the brain tissue of mice with spinal cord hemisection injury was subjected to microarray analysis. The mRNA expression levels of olfactory receptors in the brain began to decline at 8 h post-SCI. SCI promoted neuroinflammation, downregulated the expression of olfactory receptors, decreased the number of neural stem cells (NSCs), and inhibited the production of neurotrophic factors in the olfactory bulbs at 8 h post-SCI. In particular, the SCI group had upregulated mRNA and protein expression levels of glial fibrillary acidic protein (GFAP; a marker of astrocyte reactivation) and pro-inflammatory mediators [IL-1ß, IL-6, and Nestin (marker of NSCs)] in the olfactory bulb compared to levels in the sham control group. The mRNA expression levels of olfactory receptors (Olfr1494, Olfr1324, Olfr1241, and Olfr979) and neurotrophic factors [brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor (NGF)] were downregulated in the olfactory bulb of the SCI group mice at 8 h post-SCI. The administration of granulocyte colony-stimulating factor (G-CSF) mitigated these SCI-induced pathological changes in the olfactory bulb at 8 h post-SCI. These results indicate that the olfactory bulb is vulnerable to environmental damage even if the lesion is located at sites distant from the brain, such as the spinal cord. Additionally, SCI initiated pathological processes, including inflammatory response, and impaired neurogenesis, at an early stage. The findings of this study will provide a basis for future studies on pathological mechanisms of early neurodegenerative diseases involving the olfactory bulb and enable early clinical drug intervention.

The effect of different colored light emitting diode illumination on egg laying performance, egg qualities, blood hormone levels and behavior patterns in Brown Tsaiya duck.

OBJECTIVE: The objective of this experiment was to investigate the effects of different colors produced by light emitting diode (LED) on Brown Tsaiya ducks. METHODS: A total of 144 female Brown Tsaiya ducks were randomly allocated into three individual cage rearing chambers with different LED illumination colors as treatments. Three different treatments were: i) white color, ii) blue color, and iii) red color. The experiment periods were from ducks 21 to 49 weeks of age, determined traits included i) egg laying performance, ii) feed intake, iii) egg shell breaking strength, iv) egg shell thickness, v) egg Haugh unit, vi) egg weight, vii) serum Estradiol and Progesterone concentration, and viii) behavior pattern. RESULTS: The results indicated that when compared with white and blue color, red color could stimulate ducks sexual maturation and raised the egg laying performance. The red light group was also observed to have the highest feed intake among three treatments. The blue treatment had the lowest egg shell breaking strength and the highest egg weight among three treatments, nevertheless, no significant difference was observed among three treatments on egg shell thickness and egg Haugh unit. The red light group had higher serum estradiol concentration than the white and blue groups, but no significant difference among treatments on the serum Progesterone concentration was found. The results of behavior pattern indicated that red light group showed more feeding and less resting behavior compared to the blue light group. CONCLUSION: We found a potential of applying red light illumination in the indoor laying duck raising system with positive results on egg laying performance and acceptable egg weight, equivalent egg qualities compared to white and blue light.

Wild Bitter Melon Exerts Anti-Inflammatory Effects by Upregulating Injury-Attenuated CISD2 Expression following Spinal Cord Injury.

BACKGROUND: Spinal cord injuries (SCIs) induce secondary neuroinflammation through astrocyte reactivation, which adversely affects neuronal survival and eventually causes long-term disability. CDGSH iron sulfur domain 2 (CISD2), which has been reported to be involved in mediating the anti-inflammatory responses, can serve as a target in SCI therapy. Wild bitter melon (WBM; Momordica charantia Linn. var. abbreviata Ser.) contains an anti-inflammatory agent called alpha-eleostearic acid (α-ESA), a peroxisome proliferator-activated receptor-ß (PPAR-ß) ligand. Activated PPAR-ß inhibits the nuclear factor κB (NF-κB) signaling pathway via the inhibition of IκB (inhibitor of NF-κB) degradation. The role of astrocyte deactivation and CISD2 in anti-inflammatory mechanisms of WBM in acute SCIs is unknown. MATERIALS AND METHODS: A mouse model of SCI was generated via spinal cord hemisection. The SCI mice were administered WBM intraperitoneally (500 mg/kg bodyweight). Lipopolysaccharide- (LPS-) stimulated ALT cells (astrocytes) were used as an in vitro model for studying astrocyte-mediated inflammation post-SCI. The roles of CISD2 and PPAR-ß in inflammatory signaling were examined using LPS-stimulated SH-SY5Y cells transfected with si-CISD2 or scramble RNA. RESULTS: WBM mitigated the SCI-induced downregulation of CISD2, PPAR-ß, and IκB and upregulation of glial fibrillary acidic protein (GFAP; marker of astrocyte reactivation) in the spinal cord of SCI mice. Additionally, WBM (1 µg/mL) mitigated LPS-induced CISD2 downregulation. Furthermore, SH-SY5Y neural cells with CISD2 knockdown exhibited decreased PPAR-ß expression and augmented NF-κB signaling. CONCLUSION: To the best of our knowledge, this is the first study to report that CISD2 is an upstream modulator of the PPAR-ß/NF-κB proinflammatory signaling pathway in neural cells, and that WBM can mitigate the injury-induced downregulation of CISD2 in SCI mice and LPS-stimulated ALT astrocytes.

An investigation of the correlation between the S-glutathionylated GAPDH levels in blood and Alzheimer's disease progression.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by two aggregates, namely, amyloid-ß (Aß) plaques and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein (tau-p), which are released into the blood in a very small amount and cannot be easily detected. An increasing number of recent studies have suggested that S-glutathionylated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is highly correlated with Aß in patients with AD and that S-glutathionylated GAPDH plays a role as a proapoptotic factor in AD. We found that S-glutathionylated GAPDH is abundant in the blood of AD patients, which is unusual because S-glutathionylated GAPDH cannot exist in the blood under normal conditions. The aim of this study was to further explore the correlation between the S-glutathionylated GAPDH levels in blood plasma and AD progression. As controls, we recruited 191 people without AD, which included 111 healthy individuals and 37 patients with depression and insomnia, in the psychosomatic clinic. Moreover, 47 patients with AD (aged 40-89 years) were recruited at the neurology clinic. The blood S-glutathionylated GAPDH levels in the AD patients were significantly (p < 0.001) higher (752.7 ± 301.7 ng/dL) than those in the controls (59.92 ± 122.4 ng/dL), irrespective of gender and age. For AD diagnosis, the criterion blood S-glutathionylated GAPDH level > 251.62 ng/dL exhibited 95.74% sensitivity and 92.67% specificity. In fact, the individuals aged 70-89 years, namely, 37 patients from the psychosomatic clinic and 42 healthy individuals, showed significant blood S-glutathionylated GAPDH levels (230.5 ± 79.3 and 8.05 ± 20.51 ng/dL, respectively). This finding might indicate neurodegenerative AD progression in psychosomatic patients and suggests that the degree of neuronal apoptosis during AD progression might be sensitively evaluated based on the level of S-glutathionylated GAPDH in blood.

Blood glucose is a representative of the clustered indicators of multi-organ injury for predicting mortality of COVID-19 in Wuhan, China

BackgroundConcomitance with diabetes is associated with high mortality in critical conditions. Patients with previous diabetes are more vulnerable to COVID-19. However, new-onset COVID-19-related diabetes (CRD) and its relevance have scarcely been reported. This study investigates new-onset CRD and its correlation with poor outcomes or death in patients with COVID-19. MethodsWe performed a single center, retrospective case series study in 120 patients with laboratory confirmed COVID-19 at a university hospital. Fasting blood glucose (FBG) [≥]7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as CRD. The Critical status was defined as admitted to intensive care unit (ICU) or death. ResultsAfter excluding patients with a history of diabetes, chronic heart, kidney, and liver disease, 69 patients with COVID-19 were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). The prevalence of CRD in Critical and Moderate+Severe patients was 53.85% and 13.95%, respectively. Kaplan-Meier survival analysis revealed a significantly higher mortality rate in patients with CRD (P=0.0019). Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Cluster analysis suggested that indicators for multi-organ injury were interdependent, and more proximities of FBG with indicators for multi-organ injury was present. ConclusionOur results suggest that new onset COVID-19-related diabetes is an indicator of multi-organ injury and predictor for poor outcomes and death in COVID- 19 patients. As it is easy to perform for clinical practices and even self-monitoring, glucose testing will be much helpful for predicting poor outcomes to facilitate appropriate intensive care in patients with COVID-19. FundingNational Key Research and Development Program of China; The Beijing Science and Technology Project. Significance of this studyO_ST_ABSEvidence before this studyC_ST_ABSConcomitance with diabetes is associated with high mortality in critical conditions. Patients with previous diabetes are more vulnerable to COVID-19. However, new-onset COVID-19-related diabetes (CRD) and its relevance have scarcely been reported. Recently, an international group of leading diabetes researchers participating in the CoviDIAB Project have established a global registry of patients with Covid-19-related diabetes (covidiab.e-dendrite.com). Added value of this study?New-onset diabetes in COVID-19 defined as CRD was investigated. Correlation between CRD and poor outcomes or death in patients with COVID-19 was found. About half of the Critical patients have new onset CRD. CRD is the representative of the clustered indicators of multi-organ injury and is the predictor for poor outcomes and death. How might these results change the focus of research or clinical practice?Our results suggest that new onset diabetes is an indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. The study of CRD may also uncover novel mechanisms of disease.

The mediating effects of leisure engagement on relationships between caregiving stress and subjective wellbeing among family caregivers of persons with cognitive impairment: A cross-sectional study.

Family caregivers of persons with cognitive impairment experience changes in reductions in leisure engagement, which can decrease their subjective wellbeing (leisure satisfaction, negative affect and positive affect). We recruited 100 dyads of patients with cognitive impairment and family caregivers by convenience sampling from outpatient memory clinics and daycare centers in northern Taiwan. Hierarchical regression analysis tested the mediating effects of leisure engagement on the relationship between caregiving stress and subjective wellbeing. Results indicated that the restorative experience of event/tourism activities (ß = 0.23, p < .05) significantly mediated between caregiving stress and leisure satisfaction. In addition, the only significant mediator between caregiving stress and negative affect was leisure barriers (ß = 0.21, p < .05). Both of the regression models explained 27% of the variance. Future development of leisure interventions should focus on reducing leisure barriers and providing event and tourism activities to the dyads. (146 words).

Apoptosis of Tca8113 cell induced by antitumor component-I from Agkistrodon acutus venom through CHOP/Caspase-12 pathway / 中国临床药理学与治疗学

AIM: To investigate the effect of endoplasmic reticulum stress pathway on the apoptosis of tongue squamous cancer Tca8113 cells induced by antitumor component-I from Agkistrodon acutus venom (AAVC-I). METHODS: The in vitro experiments were performed on subculture tongue squamous cancer Tca8113 cells in their growth period. A normal control group, a DL-dithiothreitol (DTT) positive control group and different AAVC-I concentrations were set according to the experiment objective. MTT assay was used to detect the proliferation inhibition of Tca8113 cells after been treated with different concentrations of DTT and AAVC-I for 24 h. The results were used to choose appropriate concentrations of DTT and AAVC-I in DTT positive control group and AAVC-I treated group, respectively. HE staining and Annexin V-FITC/PI double fluorescence staining were used to monitor the apoptosis of Tca8113 cells. Western blot was used to identify the expression levels of apoptosis-related proteins including endoplasmic reticulum stress glucose-regulatory protein 78 (GRP78), enhance-binding protein-homologousprotein (CHOP), cysteine-containing aspartate specific protease-12 (Caspase-12), cysteine-containing aspartate specific protease-9 (Caspase-9) and cysteine-containing aspartate specific protease-3 (Caspase-3).RESULTS:The proliferation inhibition of Tca8113 cells increased with an increased concentration of AAVC-I concentration (P<0.05), causing cell shrinkage, increased cell gaps, cytonuclear condensation, cell fragmentation, the appearance of apoptotic bodies, and increased rate of apoptosis (P<0.05). In addition, the expression level of GRP78 protein, CHOP protein, proteins of Caspase-12, Caspase-9 and Caspase-3 were increased (P<0.05).CONCLUSION: Endoplasmic reticulum stress CHOP/Caspase-12 pathway plays an important role in AAVC-I induced Tca8113 cells apoptosis.

Kinematic Analysis of Postural Stability During Ballet Turns (pirouettes) in Experienced and Novice Dancers.

Turning is an important but difficult movement, often performed in ballet choreography. Understanding the postural sway during ballet turns is beneficial to both dancers and dance teachers alike. Accordingly, this study evaluated the postural sway angle during ballet turns in female novice and experienced ballet dancers by means of the inclination angle, determined from the center of mass (COM) and center of pressure (COP). Thirteen experienced dancers and 13 novice dancers performed ballet turns (pirouettes). The COM-COP inclination angle was measured during the preparatory, double-leg support, and single-leg support phases of the turn. The novice dancers exhibited significantly greater ranges of the COM-COP inclination angle in the anterior-posterior (AP) and medial-lateral (ML) directions during the preparatory (AP direction, p < 0.001; ML direction p = 0.035), double-leg support (AP direction p < 0.038; ML direction p = 0.011), and ending phases (AP direction p < 0.001; ML direction p = 0.024). Moreover, during the preparatory phase, the novice dancers failed to adjust their posture in a timely manner, and therefore showed overshooting errors. Finally, during the ending phase, the novice dancers showed a greater standard deviation of the COM-COP inclination angles and performed continual postural adjustments, leading to a less smooth movement than the experienced dancers. In conclusion, the novice dancers were suggested to focus on the COM-COP adjustment during both preparatory and ending phases.

Portal vein gas and pneumatosis intestinalis: A case of intestinal necrosis caused by acute organophosphorus pesticide poisoning?

Acute organophosphorus pesticide poisoning (AOPP) is fairly common in rural areas of Asia. The symptoms of AOPP are mainly caused by acetylcholine accumulation. According to the clinical characteristics, AOPP symptoms can fall into the following three categories: muscarinic, nicotinic, and central. Death from fatal poisoning is caused by respiratory paralysis, and neurological complications are common. However, no case of intestinal necrosis caused by AOPP has been reported. Hepatic portal vein gas and pneumatosis intestinalis are considered typical and early imaging manifestations of intestinal necrosis. In this article, we describe a very rare case of computed tomography imaging-proven intestinal necrosis caused by AOPP.

Protective Effects of CISD2 and Influence of Curcumin on CISD2 Expression in Aged Animals and Inflammatory Cell Model.

BACKGROUND: Inflammation and mitochondrial dysfunction have been linked to trauma, neurodegeneration, and aging. Impairment of CISD2 expression may trigger the aforementioned pathological conditions in neural cells. We previously reported that curcumin attenuates the downregulation of CISD2 in animal models of spinal cord injury and lipopolysaccharide (LPS)-treated neuronal cells. In this study, we investigate (1) the role of CISD2 and (2) how curcumin regulates CISD2 in the aging process. MATERIALS AND METHODS: The serial expression of CISD2 and the efficacy of curcumin treatment were evaluated in old (104 weeks) mice and long-term cultures of neural cells (35 days in vitro, DIV). LPS-challenged neural cells (with or without siCISD2 transfection) were used to verify the role of curcumin on CISD2 underlying mitochondrial dysfunction. RESULTS: In the brain and spinal cord of mice aged P2, 8, 25, and 104 weeks, we observed a significant decrease in CISD2 expression with age. Curcumin treatment in vivo and in vitro was shown to upregulate CISD2 expression; attenuate inflammatory response in neural cells. Moreover, curcumin treatment elevated CISD2 expression levels and prevented mitochondrial dysfunction in LPS-challenged neural cells. The beneficial effects of curcumin in either non-stressed or LPS-challenged cells that underwent siCISD2 transfection were significantly lower than in respective groups of cells that underwent scrambled siRNA-transfection. CONCLUSIONS: We hypothesize that the protective effects of curcumin treatment in reducing cellular inflammation associated trauma, degenerative, and aging processes can be partially attributed to elevated CISD2 expression. We observed a reduction in the protective effects of curcumin against injury-induced inflammation and mitochondrial dysfunction in cells where CISD2 expression was reduced by siCISD2.

Treatment of Arsenite Intoxication-Induced Peripheral Vasculopathy with Mesenchymal Stem Cells.

Arsenite (As), a notorious toxic metal, is ubiquitously distributed in the earth and poses a serious threat to human health. Histopathological lesions of As intoxication are known as thromboangiitis obliterans, which are resistant to current treatment and often lead to lower limb amputation. In this study, we attempt to find that treatment with mesenchymal stem cells (MSCs) may be effective for As-induced vasculopathy. We first conducted an in vitro study with a co-culture system containing human MSCs and human umbilical vein endothelial cells (HUVECs) and treated individual and co-cultured cells with various concentrations of arsenite. We also designed an in vivo study in which Sprague Dawley (SD) rats received periodic intraperitoneal (IP) injections of 16 ppm arsenite for 12 weeks. MSCs were harvested from BALB/c mice that were transplanted via tail vein injection. We found that there was significantly higher cellular viability in human mesenchymal stem cells (hMSCs) than in HUVECs under concentrations of arsenite between 15 and 25 µM. The Annexin V apoptosis assay further confirmed this finding. Cytokine array assay for As-conditioned media revealed an elevated vascular endothelial growth factor (VEGF) level secreted by MSCs, which is crucial for HUVEC survival and was evaluated by an siRNA VEGF knockdown test. In the in vivo study, we demonstrated early apoptotic changes in the anterior tibial vessels of As-injected SD rats with a Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, but these apoptotic changes were less frequently observed upon MSCs transplantation, indicating that the cytoprotective effect of MSCs successfully protected against As-induced peripheral vasculopathy. The feasibility of MSCs to treat and /or prevent the progression of As-induced vasculopathy is justified. Further clinical studies are required to demonstrate the therapeutic efficacy of MSCs in patients suffering from As intoxication with vasculopathy.

Growing pigs developed different types of diabetes induced by streptozotocin depending on their transcription factor 7-like 2 gene polymorphisms.

The different polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene promote variances in diabetes susceptibility in humans. We investigated whether these genotypes also promote differences in diabetic susceptibility in commercial pigs. Growing pigs (Landrace, both sex, 50-60 kg) with the C/C (n=4) and T/T (n=5) TCF7L2 genotypes were identified and intravenously injected with streptozotocin (STZ, 40 mg/kg) twice in weekly intervals, then a high-energy diet was offered. Oral glucose tolerance tests, blood analyses and the homeostasis model assessment-insulin resistance (HOMA-IR) index calculations were performed. The animals were sacrificed at the end of 12 weeks of treatment to reveal the pancreas histomorphometry. The results showed that all of the treated pigs grew normally despite exhibiting hyperglycemia at two weeks after the induction. The glycemic level of the fasting or postprandial pigs gradually returned to normal. The fasting insulin concentration was significantly decreased for the T/T carriers but not for the C/C carriers, and the resulting HOMA-IR index was significantly increased for the C/C genotype, indicating that the models of insulin dependence and resistance were respectively developed by T/T and C/C carriers. The histopathological results illustrated a significant reduction in the pancreas mass and insulin active sites, which suggested increased damage. The results obtained here could not be compared with previous studies because the TCF7L2 background has not been reported. Growing pigs may be an excellent model for diabetic in children if the animals are genetically pre-selected.

Tumoral calcinosis misdiagnosed

Tumoral calcinosis is an uncommon condition which has been described to exist in primary and secondary forms. A lack of awareness of this entity can lead to unnecessary procedures and incorrect management. We report a case of a patient on peritoneal dialysis who presented with multiple painful joint swellings to the orthopaedic department. An initial diagnosis of septic arthritis was made, then revised to chronic tophaceous gout and referred to the rheumatology unit.

Neuro-fuzzy method for predicting the viability of stem cells treated at different time-concentration conditions.

Dental stem cells isolated for human dental pulp are an excellent source for regenerative medicine and dentistry. Simulation of clinical scenario is one of the crucial challenges for evaluation of the efficacy of DPSCs in various regenerative therapies. In this study we evaluated the viability of DPSCs after treatment with artificial bacterial lipopolysaccharides (LPS) as the main component responsible for inducing inflammatory response in majority of the inflammatory conditions in clinical scenario. Although a number of studies have previously treated stem cells with LPS from bacteria, however the accuracy level of the outcome was not established. Here we have analyzed the outcome using adaptive neuro-fuzzy inferences system (ANFIS) to predict the viability of human DPSCs after treatment with bacterial LPS.