Stress Protein Levels Research Articles

Real-Time Suture Reconstruction in Rat Skin Stretching Experiments With Multiocular Stereo Vision Measurement System

To investigate the effects of skin stretching stress on tissue expansion and its mechanotransduction mechanism, an animal model of skin stretching was established in our previous work. However, the distribution of stress in the skin cannot be precisely determined in real-time, which leads to an imprecise correlation analysis between stress distribution and protein levels of mechanosensitive molecules. To address this problem, a real-time suture reconstruction method with a multi-ocular stereo vision measurement system was developed in this study. The shape of the suture passing through the rat’s skin can be measured in real-time, and the distribution of skin stress can be precisely determined. The key to real-time suture reconstruction is suture-matching in multi-ocular images, therefore a suture-matching method based on the nearest-neighbor rule and region growing was proposed. First, color markers were fixed on the suture nodes and the frame, secondly, pixels in the frame region are sampled, and the frame inner region is segmented by the nearest neighbor rule. Furthermore, the pixels within the color markers in the region were selected as the seed points for growth, and the markers were segmented using a edge and color integrated detection method. Finally, the markers on the frame were fitted to form a reference line, and the distance between each marker on the suture and the reference line was calculated as the matching feature to realize image matching of nodes in the stereo camera. The three-dimensional coordinates of the nodes were calculated based on region growth, and the sutures were reconstructed using a B-spline curve. The experimental results confirmed the feasibility and high robustness of the proposed method, which ensured accurate three-dimensional reconstruction of the suture.

The Role of Mindfulness in Promoting Subjective Wellbeing and Mood Homeostasis in Patients with Crohn’s Disease

Background: The relationship between stress, symptoms of inflammatory bowel disease (IBD), and depression has not previously been considered using the theory of subjective wellbeing (SWB) homeostasis as a conceptual framework. It is proposed that mindfulness, as a mechanism of down-regulating challenging emotion, can aid in the restoration of mood homeostasis and reduce symptoms of both psychological and physiological stress. The study aims to identify whether individuals with Crohn’s disease (CD) and co-occurring psychological depression or stress are experiencing the defeat of SWB homeostasis. Further, the study aims to test whether a Mindfulness Based Stress Reduction (MBSR) intervention can restore homeostasis. The study would also identify whether this restoration of homeostasis is associated with a reduction in disease symptomatology.
 Methods/Design: An exploratory randomised control trial with 40 participants recruited from public health gastroenterology patients and randomly allocated to an 8-week MBSR program or wait-list control. Measures of SWB, depression, stress, and C-reactive protein (CRP) levels will be collected prior to and after the intervention. Individual HPMood set points will be determined from affect data collected over 7 days through momentary sampling techniques prior to the commencement of the intervention. Measures will be repeated at 6-month follow-up. Following this, the wait-list group will be offered the same 8-week MBSR. Hypotheses will be tested using mixed ANOVA and clinical significance tests.
 Discussion: This study will be an important contributor to knowledge about psychological vulnerability and resilience for people with CD and will provide initial evidence that could contribute to the development of a larger future trial.

Relationship Between Oxidative Stress, Tau Level and Antioxidant Mechanisms of the KEAP-1/NRF-2/HO-1 in Children with Hydrocephalus.

Hydrocephalus is a complex neurologic disorder that has a widespread impact on the central nervous system and a multifactor disease which affects the CSF dynamics and causes severe neurological impairments in children. The pathophysiology of hydrocephalus is not fully understood. However, increasing evidence suggests that oxidative stress may be an important factor in the pathogenesis of hydrocephalus. The purpose of this study is to investigate the relationship of the KEAP-1/NRF-2/HO-1 pathway, one of the main regulators of the antioxidant system in the hydrocephalus pathology, on oxidative stress and tau protein level. The study included 32 patients with hydrocephalus and 32 healthy controls. KEAP-1, NRF-2, HO-1, TAU, and MPO levels are measured using ELISA method TAS, TOS, and Total THIOL colorimetric method. KEAP-1, TAS, and Total THIOL levels were found significantly lowerer in the hydrocephalus group than in the control group. Nevertheless, it was identified that in the hydrocephalus group that the NRF-2, HO-1, TAU, MPO, TOS, and OSI levels were significantly elevated. In conclusion, although the KEAP-1/NRF-2/HO-1 pathway is activated in patients with hydrocephalus, it is identified that the antioxidant defense system is insufficient and ultimately leads to elevated oxidative stress. The elevation in the tau level may be an indicator of oxidative stress induced neurodegenerative damage.

Inhibition of endoplasmic reticulum stress reverses synaptic plasticity deficits in striatum of DYT1 dystonia mice.

Background and objective: Striatal plasticity alterations caused by endoplasmic reticulum (ER) stress is supposed to be critically involved in the mechanism of DYT1 dystonia. In the current study, we expanded this research field by investigating the critical role of ER stress underlying synaptic plasticity impairment imposed by mutant heterozygous Tor1a+/- in a DYT1 dystonia mouse model.Methods: Heterozygous Tor1a+/- mouse model for DYT1 dystonia was established. Wild-type (Tor1a+/+, N=10) and mutant (Tor1a+/-, N=10) mice from post-natal day P25 to P35 were randomly distributed to experimental and control groups. Patch-clamp and current-clamp recordings of SPNs were conducted with intracellular electrodes for electrophysiological analyses. Striatal changes of the direct and indirect pathways were investigated via immunofluorescence. Golgi-Cox staining was conducted to observe spine morphology of SPNs. To quantify postsynaptic signaling proteins in striatum, RNA-Seq, qRT-PCR and WB were performed in striatal tissues.Results: Long-term depression (LTD) was failed to be induced, while long-term potentiation (LTP) was further strengthened in striatal spiny projection neurons (SPNs) from the Tor1a+/- DYT1 dystonia mice. Spine morphology analyses revealed a significant increase of both number of mushroom type spines and spine width in Tor1a+/- SPNs. In addition, increased AMPA receptor function and the reduction of NMDA/AMPA ratio in the postsynaptic of Tor1a+/- SPNs was observed, along with increased ER stress protein levels in striatum of Tor1a+/- DYT1 dystonia mice. Notably, ER stress inhibitors, tauroursodeoxycholic acid (TUDCA), could rescue LTD as well as AMPA currents.Conclusion: The current study illustrated the role of ER stress in mediating structural and functional plasticity alterations in Tor1a+/- SPNs. Inhibition of the ER stress by TUDCA is beneficial in reversing the deficits at the cellular and molecular levels. Remedy of dystonia associated neurological and motor functional impairment by ER stress inhibitors could be a recommendable therapeutic agent in clinical practice.

Marantodes pumilum Var Alata (Kacip Fatimah) ameliorates derangement in RANK/RANKL/OPG pathway and reduces inflammation and oxidative stress in the bone of estrogen-deficient female rats with type-2 diabetes

BackgroundM. pumilum has been claimed to protect the bone against the adverse effect of estrogen deficiency. Additionally, it also exhibits anti-diabetic activity. In view of these, this study aims to identify the mechanisms underlying the bone protective effect of M. pumilum in the presence of both estrogen deficiency and diabetes mellitus (DM). MethodsOvariectomized, diabetic female rats were given M. pumilum leave aqueous extract (MPLA) (50 and 100 mg/kg/day), estrogen, glibenclamide and estrogen plus glibenclamide for 28 consecutive days. At the end of the treatment, fasting blood glucose (FBG), serum insulin, Ca2+, PO43− and bone alkaline phosphatase (BALP) levels were measured. Rats were sacrificed and femur bones were harvested for determination of expression level and distribution of RANK, RANKL, OPG and oxidative stress and inflammatory proteins by molecular biological techniques. Results100 mg/kg/day MPLA treatment decreased the FBG and BALP levels but increased the serum insulin, Ca2+ and PO43− levels in estrogen deficient, diabetic rats. Expression and distribution of RANKL, NF-κB p65, IKKβ, IL-6, IL-1β and Keap-1 decreased however expression and distribution of RANK, OPG, BMP-2, Type-1 collagen, Runx2, TRAF6, Nrf2, NQO-1, HO-1, SOD and CAT increased in the bone of estrogen deficient, diabetic rats which received 100 mg/kg/day MPLA with greater effects than estrogen-only, glibenclamide-only and estrogen plus glibenclamide treatments. ConclusionMPLA helps to overcome the adverse effect of estrogen deficiency and DM on the bone and thus this herb could potentially be used for the treatment and prevention of osteoporosis in postmenopausal women with diabetes.

Effects of the Antidepressants Citalopram and Venlafaxine on the Big Ramshorn Snail (Planorbarius corneus)

Depression is a serious health issue and, being such, treatment for it has become a topic of increasing concern. Consequently, the prescription rates of antidepressants have increased by about 50% over the past decade. Among antidepressants, citalopram and venlafaxine are the most frequently prescribed in Germany. Due to the high consumption and low elimination rates of both antidepressants during wastewater purification, they are frequently found in surface waters, where they may pose a risk to the aquatic environment. For the present study, we conducted experiments with the big ramshorn snail, which we exposed to environmentally relevant and explicitly higher concentrations (1–1000 µg/L) of the antidepressants citalopram and venlafaxine. We investigated apical endpoints, such as weight, mortality, behavioural changes, B-esterase activity, Hsp70 stress protein level and superoxide dismutase activity, as well as the tissue integrity of the hepatopancreas in the exposed snails. Citalopram and venlafaxine had no effects on the B-esterase activity, Hsp70 level and superoxide dismutase activity. Citalopram exposure resulted in weight reduction and tissue reactions in the hepatopancreas of snails exposed to 1000 µg/L. In contrast, venlafaxine did not induce comparable effects, but impacted the behaviour (sole detachment) of snails exposed to 100 µg/L and 1000 µg/L of the antidepressant. These results revealed that venlafaxine can affect snails at concentrations 10 times lower than citalopram. For this, in 2020 venlafaxine was introduced in the “Surface Water Watch List”, a list of potential pollutants that should be carefully monitored in surface water by the EU Member States.

Melatonin pretreatment alleviates blast-induced oxidative stress in the hypothalamic-pituitary-gonadal axis by activating the Nrf2/HO-1 signaling pathway

Although melatonin has been demonstrated to exert a potent antioxidant effect, the ability of melatonin to alleviate blast-induced oxidative stress in the hypothalamic-pituitary-gonadal (HPG) axis remains unclear. This study aimed to elucidate the effects and underlying mechanism of melatonin pretreatment on the HPG axis disrupted by blast injury. Sixty C57BL/6 mice were randomly divided into control, blast, and blast + melatonin groups for behavioral experiments. The elevated maze experiment, open field experiment, and Morris Water Maze experiment were carried out on the 7th, 14th and 28th day after the blast injury. Fifty Sprague Dawley rats were randomly divided into control, blast, blast + melatonin, and blast + melatonin + luzindole groups for hormone assays and molecular and pathological experiments. Blood samples were used for HPG axis hormone detection and ELISA assays, and tissue samples were used to detect oxidative stress, inflammation, apoptosis, and stress-related protein levels. The results showed that melatonin pretreatment alleviated blast-induced behavioral abnormalities in mice and maintained the HPG axis hormone homeostasis in rats. Additionally, melatonin significantly reduced MDA5 expression and increased the expression of Nrf2/HO-1. Moreover, melatonin significantly inhibited NF-κB expression and upregulated IL-10 expression, and it reversed the blast-induced high expression of caspase-3 and Bax and the low expression of Bcl-2. Furthermore, luzindole counteracted melatonin inhibition of NF-κB and upregulated Nrf2/HO-1. Melatonin significantly alleviated blast-induced HPG axis hormone dyshomeostasis, behavioral abnormalities, oxidative stress, inflammation, and apoptosis, which may be achieved by upregulating the Nrf2/HO-1 signaling pathway. Our study suggested that melatonin pretreatment is a potential treatment for blast-induced HPG axis hormonal and behavioral abnormalities.

Salubrinal Exposes Anticancer Properties in Inflammatory Breast Cancer Cells by Manipulating the Endoplasmic Reticulum Stress Pathway.

The endoplasmic reticulum (ER) regulates protein folding, post-translational modifications, lipid synthesis, and calcium signaling to attenuate the accumulation of misfolded proteins causing ER stress and maintains cellular homeostasis. The tumor microenvironment is rich in soluble cytokines, chemokines, growth, and angiogenic factors and can drive the ER’s abnormal functioning in healthy cells. Cancer cells adapt well to the tumor microenvironment induced ER stress. We identified that the inflammatory breast cancer (IBC) cells abundantly express osteoprotegerin (OPG) and their tumor microenvironment is rich in OPG protein. OPG also called osteoclast differentiation factor/osteoclastogenesis inhibitory factor (OCIF) is a soluble decoy receptor for receptor activator of nuclear factor-kappa B ligand (RANKL). Employing mass spectrometry analysis, we identified a set of ER chaperones associated with OPG in IBC cell lysates (SUM149PT, SUM1315MO2) compared to healthy human mammary epithelial cells (HMEC). Proximity ligation assay (PLA) and immunoprecipitation assay validated the interaction between OPG and ER chaperone and master regulator of unfolded protein response (UPR) GRP78/BiP (glucose-regulated protein/Binding immunoglobulin protein). We detected remarkably high gene expression of CCAAT enhancer-binding protein homologous protein (CHOP), inositol-requiring enzyme 1 (IRE1α), protein disulfide-isomerase (PDI), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), X-box binding protein 1 (XBP-1) and growth arrest and DNA damage-inducible protein (GADD34) in SUM149PT and SUM190PT cells when compared to HMEC. Similarly, tissue sections of human IBC expressed high levels of ER stress proteins. We evaluated cell death and apoptosis upon Salubrinal and phenylbutyrate treatment in healthy and IBC cells by caspase-3 activity and cleaved poly (ADP-ribose) polymerase (PARP) protein assay. IBC (SUM149PT and SUM190PT) cells were chemosensitive to Salubrinal treatment, possibly via inhibition in OPG secretion, upregulating ATF4, and CHOP, thus ultimately driving caspase-3 mediated IBC cell death. Salubrinal treatment upregulated PDI, which connects ER stress to oxidative stress. We observed increased ROS production and reduced cell proliferation of Salubrinal treated IBC cells. Treatment with antioxidants could rescue IBC cells from ROS and aborted cell proliferation. Our findings implicate that manipulating ER stress with Salubrinal may provide a safer and tailored strategy to target the growth of inflammatory and aggressive forms of breast cancer.

Comparative analyses of extreme dry seed thermotolerance in five Cactaceae species

Extreme dry seed thermotolerance is an important trait in the context of plant adaptation to desert environments, yet the mechanisms underlying interspecific differences in seed extremophily remain little understood. Seeds of a selection of desert Cactaceae species (Leucostele litoralis, Leucostele skottsbergii, Eulychnia breviflora, Eriosyce paucicostata and Ferocactus wislizeni) were subjected to comparative biophysical and molecular analyses prior to (mature dry seeds) and post (imbibing seeds) heat treatment (103 °C).Biophysical properties of mature dry seeds, such as seed coat hardness and thermal transitions, were characterized through puncture force resistance and differential scanning calorimetry, respectively. In addition, the protein composition of dry seeds was compared by 2-D electrophoresis and de novo sequencing. Finally, oxidative DNA damage repair and gene expression during seed imbibition were analysed via ELISA (8-oxo-dG levels) and comparative transcriptomics.Results revealed that enhanced dry seed thermotolerance could not be explained by seed coat hardness, seed thermal transitions or (ROS-induced oxidative) DNA damage repair. Comparative proteomic analysis showed that the majority of overlapping proteins were more abundant in relatively heat sensitive species, suggesting that higher basal levels of (stress) proteins do not underly improved heat resilience in Cactaceae. However, comparative transcriptomics during imbibition following heat stress detected consistent expression patterns of heat- and drying-responsive genes that correlated with dry seed thermotolerance. These patterns included upregulation of positive (HSP101/CLPB1, MGE2, MBF1c, HSFB2A, RPN1a, RPT2a, DEGP14/PARK13, XPO1A, MAIGO2/MAG2, CAMTA1, ADH1) and downregulation of negative (RCF3, VOZ1, FAD7, ZAT12, RNP1) heat and drought tolerance regulators.Thus, our comparative analyses of extremophile Cactaceae species suggest that higher dry seed thermotolerance is realised through enhanced recovery from heat stress during imbibition, which is a critical stage in the plant life cycle.

The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice.

Background:Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Previous studies have indicated that particles of these products have several effects on the gut and liver. Polystyrene (PS)-MPs (PS-MPs) induce several responses, such as oxidative stress, and affect living organisms.Objectives:The aim of this study was to investigate the effects of PS-MPs in kidney cells in vitro and in vivo.Methods:PS-MPs were evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6 mice. Mitochondrial reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, inflammation, and autophagy were analyzed in kidney cells. In vivo, we evaluated biomarkers of kidney function, kidney ultrastructure, muscle mass, and grip strength, and urine protein levels, as well as the accumulation of PS-MPs in the kidney tissue.Results:Uptake of PS-MPs at different concentrations by HK-2 cells resulted in higher levels of mitochondrial ROS and the mitochondrial protein Bad. Cells exposed to PS-MPs had higher ER stress and markers of inflammation. MitoTEMPO, which is a mitochondrial ROS antioxidant, mitigated the higher levels of mitochondrial ROS, Bad, ER stress, and specific autophagy-related proteins seen with PS-MP exposure. Furthermore, cells exposed to PS-MPs had higher protein levels of LC3 and Beclin 1. PS-MPs also had changes in phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (AKT)/mitogen-activated protein kinase (mTOR) signaling pathways. In an in vivo study, PS-MPs accumulated and the treated mice had more histopathological lesions in the kidneys and higher levels of ER stress, inflammatory markers, and autophagy-related proteins in the kidneys after PS-MPs treatment by oral gavage.Conclusions:The results suggest that PS-MPs caused mitochondrial dysfunction, ER stress, inflammation, and autophagy in kidney cells and accumulated in HK-2 cells and in the kidneys of mice. These results suggest that long-term PS-MPs exposure may be a risk factor for kidney health. https://doi.org/10.1289/EHP7612

Inhibition of 12/15 Lipoxygenase (12/15 LOX) Improves Renal Recovery and Function Post Renal Ischemia Reperfusion (IR) injury in Male Spontaneous Hypertensive Rats (SHR)

Acute kidney injury (AKI) due to ischemia reperfusion (IR) is a serious complication in clinical settings and the male gender is often associated with greater severity and mortality following AKI vs. age-matched females. Recent clinical and basic science studies further suggest that renal ischemic injury increases the likelihood of developing hypertension and hypertensive subjects are likely to have greater AKI severity. Despite the widespread prevalence of hypertension and AKI, what mediates renal IR injury leading to increased risk of later developing cardiovascular and renal diseases in either sex is poorly understood. Elevated 12/15-LOX activity has been reported in hypertension and in many kidney diseases. The goal of the current study was to test the hypothesis that enhanced activation of 12/15-LOX in hypertensive males results in greater increases in endoplasmic reticulum (ER) stress and tubular cell death leading to impaired post recovery compared females following renal IR. 13-week old male and female SHR were subjected to sham or 30-minute warm bilateral IR (n=6/group). Blood and urine were collected 24 hrs and 7 days after IR; kidneys were harvested 7 days post-IR for biochemical, histological, and Western blot analysis. IR increased plasma creatinine (Pcr) and blood urea nitrogen (BUN) in both male and female SHR compared to respective sham controls at 24 hrs (PIR =0.0001; Psex*IR=0.2). At 7 days post-IR, Pcr and BUN remained elevated in male SHR but returned to baseline levels in females (Pcr: PIR =0.03; Psex*IR=0.04; BUN: PIR <0.05; Psex*IR=0.05). Histological examination of kidneys 7 days post-IR showed increases in damaged tubules (PIR=0.0003, Psex*IR=0.0019) and tubular cell death (PIR=0.001; Psex*IR=0.001) in males vs. females SHR. Delayed recovery of renal function in male SHR was associated with an upregulation of renal 12/15-LOX protein (PIR<0.05; Psex*IR=0.008), increased lipid peroxidation (PIR=0.008; Psex*IR=0.018), and ER stress protein levels (PIR=0.05; Psex*IR=0.01) compared to sham-controls. To assess the contribution of 12/15 LOX on impaired recovery from IR in male SHR, additional rats were randomized to receive vehicle or the specific 12/15-LOX inhibitor ML355 (30 mg/kg i.p.; n=5/group) 1 hr prior to sham/IR and every other day up to 7 days. Treatment with ML355 1) reduced lipid peroxidation (PIR*TxT =0.02) and ER stress protein levels (PIR*TxT =0.05), 2) prevented IR-induced tubular damage (PIR*TxT=0.02) and tubular cell death (PIR*TxT=0.04), and 3) improved renal function (Pcr: PIR*TxT =0.0067; BUN: PIR*TxT =0.042) compared to vehicle-treated males following IR. In conclusion, our data demonstrate that enhanced activation of 12/15-LOX in the kidney contributes to impaired renal recovery post-IR in male SHR.

Wound-Induced Changes in Antioxidant Enzyme Activities in Skin Mucus and in Gene Expression in the Skin of Gilthead Seabream (Sparus aurata L.)

This study investigated the antioxidant enzyme activities in the skin mucus of gilthead seabream (Sparus aurata L.) at 3 and 7 days post-wounding (dpw). The expression levels of the genes that encode stress proteins (grp170, grp94, grp75, sod and hsp70) and skin regeneration-related proteins (tf, igf1, tgfb1, der1, apo1 and erdj3) in the skin also were determined. Mucus and skin samples were obtained from the left and right flanks of non-wounded and wounded fish. In both flanks of the wounded fish, catalase and glutathione reductase activities in the skin mucus increased (p &lt; 0.05) at 3 and 7 dpw (100 ± 31% and 111 ± 25%, respectively), whereas superoxide dismutase activity increased (p &lt; 0.05) only at 7 dpw (135 ± 15%). The expression levels of stress proteins in the skin of the wounded flank of the wounded fish mainly increased at 7 dpw (grp170 increased to 288 ± 85%, grp94 to 502 ± 143%, grp75 to 274 ± 69%, sod to 569 ± 99%, and hsp70 increased to 537 ± 14%) (p &lt; 0.05). However, the expression levels of the tissue regeneration-related genes varied depending on the flank investigated, on the experimental time, and on the gene studied. To the best of our knowledge, this is the first work to determine the effect of a wound in different skin parts of the same fish.

Ginkgolide B‑induced AMPK pathway activation protects astrocytes by regulating endoplasmic reticulum stress, oxidative stress and energy metabolism induced by Aβ1‑42

Ginkgolide B (GB), the diterpenoid lactone compound isolated from the extracts of Ginkgo biloba leaves, significantly improves cognitive impairment, but its potential pharmacological effect on astrocytes induced by β-amyloid (Aβ)1-42 remains to be elucidated. The present study aimed to investigate the protective effect and mechanism of GB on astrocytes with Aβ1-42-induced apoptosis in Alzheimer's disease (AD). Astrocytes obtained from Sprague Dawley rats were randomly divided into control, Aβ, GB and GB + compound C groups. Cell viability and apoptosis were analyzed using Cell Counting Kit-8 and flow cytometry assays, respectively. Protein and mRNA expression levels were analyzed using western blotting and reverse transcription-quantitative PCR, respectively. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), reactive oxygen species (ROS) and ATP were determined using the corresponding commercial kits. The findings revealed that GB attenuated Aβ1-42-induced apoptosis and the 5′ adenosine monophosphate- activated protein kinase (AMPK) inhibitor compound C reversed the protective effects of GB. In addition, GB reversed Aβ1-42-induced oxidative damage and energy metabolism disorders, including decreases in the levels of SOD, GSH-Px and ATP and increased the levels of MDA and ROS in astrocytes, while compound C reversed the anti-oxidative effect and the involvement of GB in maintaining energy metabolism in astrocytes. Finally, GB decreased the expression levels of the endoplasmic reticulum stress (ERS) proteins and the apoptotic protein CHOP and increased both mRNA and protein expression of the components of the energy metabolism-related AMPK/peroxisome proliferator-activated receptor γ coactivator 1α/peroxisome proliferator-activated receptor α and anti-oxidation-related nuclear respiratory factor 2/heme oxygenase 1/NAD(P)H dehydrogenase (quinone 1) pathways and downregulated the expression of β-secretase 1. However, compound C could antagonize these effects. In conclusion, the findings demonstrated that GB protected against Aβ1-42-induced apoptosis by inhibiting ERS, oxidative stress, energy metabolism disorders and Aβ1-42 production probably by activating AMPK signaling pathways. The findings provided an innovative insight into the treatment using GB as a therapeutic in Aβ1-42-related AD.

Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats.

To investigate the effects of radiation on rat submandibular glands and the possible protective effects of ischemic preconditioning, the submandibular glands of Wistar rats were subjected to in situ radiation after ischemic preconditioning. The glands were exposed to X-radiation at a single dose of 20Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro-inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12weeks post-irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin-5 levels were lower at 1 and 12weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor-α, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin-4 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury-stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation-induced injury to submandibular glands and ameliorated salivary hyposecretion.

Irigenin alleviates angiotensin II-induced oxidative stress and apoptosis in HUVEC cells by activating Nrf2 pathway.

Endothelial dysfunction is closely related to various cardiovascular diseases. Oxidative stress and apoptosis are involved in the progress of endothelial dysfunction. Irigenin (IR) has antioxidative properties. We investigated IR as a novel therapy for angiotensin II (Ang II)-induced endothelial dysfunction and explored the potential mechanisms of IR. After human umbilical vein endothelial cell lines (HUVECs) were treated with Ang II (100, 200, 300 and 400 nmol/L) alone, IR (2.5, 5, 10, 20 and 40 μmol/L) alone or Ang II plus IR for 24 h, HUVECs viability, lactate dehydrogenase (LDH), apoptosis, oxidative stress, apoptosis-related protein and nuclear factor E2-related factor 2 (Nrf2) levels were detected by Cell Counting Kit (CCK)-8 assay, enzyme-linked immunosorbent assay, flow cytometry and western blot. Transfection rate of Nrf2 was detected by western blot. In the next rescue experiment, we used silent Nrf2 (siNrf2) to verify the previous experimental results. Different concentrations' Ang II repressed HUVECs viability and increased LDH release, and different concentrations' IR did not affect HUVECs viability or LDH release. Furthermore, IR elevated cell viability and Nrf2 level, inhibited LDH release, apoptosis, oxidative stress and apoptosis-related protein levels in Ang II-induced HUVECs. More important, siNrf2 suppressed the expression of Nrf2, and siNrf2 abrogated the protective effect of IR on Ang II-induced Nrf2 expression, cell viability, LDH activity, oxidative stress generation and apoptosis-related protein in HUVECs. IR protected HUVECs from Ang II-induced oxidative stress and apoptosis injury by activating Nrf2 pathway.

Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells.

Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.

Using mobile sensing data to assess stress: Associations with perceived and lifetime stress, mental health, sleep, and inflammation.

BackgroundAlthough stress is a risk factor for mental and physical health problems, it can be difficult to assess, especially on a continual, non-invasive basis. Mobile sensing data, which are continuously collected from naturalistic smartphone use, may estimate exposure to acute and chronic stressors that have health-damaging effects. This initial validation study validated a mobile-sensing collection tool against assessments of perceived and lifetime stress, mental health, sleep duration, and inflammation.MethodsParticipants were 25 well-characterized healthy young adults (Mage = 20.64 years, SD = 2.74; 13 men, 12 women). We collected affective text language use with a custom smartphone keyboard. We assessed participants’ perceived and lifetime stress, depression and anxiety levels, sleep duration, and basal inflammatory activity (i.e. salivary C-reactive protein and interleukin-1β).ResultsThree measures of affective language (i.e. total positive words, total negative words, and total affective words) were strongly associated with lifetime stress exposure, and total negative words typed was related to fewer hours slept (all large effect sizes: r = 0.50 – 0.78). Total positive words, total negative words, and total affective words typed were also associated with higher perceived stress and lower salivary C-reactive protein levels (medium effect sizes; r = 0.22 – 0.32).ConclusionsData from this initial longitudinal validation study suggest that total and affective text use may be useful mobile sensing measures insofar as they are associated with several other stress, mental health, behavioral, and biological outcomes. This tool may thus help identify individuals at increased risk for stress-related health problems.

Protective effects of Gamma Oryzanol on distant organs after kidney ischemia-reperfusion in rats: A focus on liver protection.

Acute kidney injury (AKI) is the main clinical concern resulted from ischemia-reperfusion injury (IRI). Ample clinical data indicates that AKI is associated with distant organ dysfunctions and poor patients' outcomes. Oxidative stress and inflammation have a critical role in the pathogenesis of organ injuries following IRI. The objectives of this study were to determine the impact of Gamma Oryzanol (GO), extracted from rice bran oil, on distant organs in rats after IRI. Twelve out of 24 Wistar rats were treated by one dosage of GO (100mg/kg) 1 h before I/R induction through both oral gavage and intraperitoneal injection. Then, the AKI model rats were induced by IRI. Oxidative stress and antioxidant protein levels were assessed in the brain, heart, and liver tissues in the experimental groups. Furthermore, the effects of GO on IRI-induced liver dysfunction, apoptosis, and inflammation were measured by Western blot. GO pretreatment could significantly restore the levels and activity of antioxidant proteins in the brain, heart, and liver tissues (P < 0.05). Moreover, GO pretreatment could decrease the inflammatory cytokine (IL-1, IL-6, and TNF-α) in the liver (P < 0.01). By reducing Bax/Bcl-2 ratio and down-regulating caspase-3, GO could significantly diminish apoptosis in the liver tissue after the kidney I/R (P < 0.01). Additionally, GO could significantly diminish the deterioration of liver function in the kidney I/R model. GO protects distant organs against renal IRI-induced oxidative stress. Furthermore, it ameliorates liver function and remarkably exerts anti-oxidative, anti-inflammatory, and anti-apoptotic roles in the liver as an important detoxifying organ.

Biochemical and cellular biomarkers in brown trout (Salmo trutta f. fario) in response to the antidepressants citalopram and venlafaxine

BackgroundDuring the last decades, a worldwide increase in the number of cases of depression accompanied by rising prescription rates of antidepressants was recorded. In Germany, the two most prescribed antidepressants are the selective serotonin reuptake inhibitor (SSRI) citalopram and the serotonin and noradrenalin reuptake inhibitor (SNRI) venlafaxine, taking about 30% of the market share. Both antidepressants are found frequently in surface waters and have the potential of adversely affecting aquatic organisms. Most studies dealing with antidepressants address apical endpoints and behaviour; however, only few studies investigate biochemical biomarkers and histopathological alterations. We conducted citalopram and venlafaxine exposure experiments over 5 months, starting with brown trout eggs in the eyed-ova stage, as well as with juvenile brown trout for 4 weeks. Exposure concentrations ranged from environmentally relevant 1 µg/L up to 1 mg/L. In this study, we investigated the effects of the antidepressants on b-esterase activity (neurotoxicity), stress protein level (proteotoxicity) and superoxide dismutase activity (oxidative stress). Additionally, we assessed the health status of the liver by means of histopathological analyses.ResultsWe were able to show that both antidepressants did neither induce proteotoxic nor neurotoxic effects in brown trout. But for venlafaxine, the biochemical biomarker for oxidative stress (superoxide dismutase activity) was significantly increased in larvae exposed to at least 10-µg/L venlafaxine at 7 °C. With regard to liver histopathology, fish exposed to higher citalopram concentrations were in a worse health condition than control fish irrespective of their life stage. Also, the energy storage of fish exposed to 1 mg/L citalopram was reduced.ConclusionThus, we here report citalopram-dependent histopathological alterations in brown trout liver, and the induction of oxidative stress by venlafaxine.

Activation of the ROS/HO-1/NQO1 signaling pathway contributes to the copper-induced oxidative stress and autophagy in duck renal tubular epithelial cells

The aim of this study was to investigate the crosstalk between oxidative stress and autophagy through the ROS/HO-1/NQO1 pathway caused by copper (Cu). Duck renal tubular epithelial cells were treated in Cu sulfate (CuSO4) (0, 100 and 200 μM) for 12 h, and in the combination of CuSO4 (200 μM) and reactive oxygen species (ROS) scavenger (butyl hydroxyanisole, BHA, 100 μM), or HO-1 inhibitor (zinc protoporphyrin, ZnPP, 10 μM) for 12 h. Results revealed that Cu could significantly elevate the levels of intracellular ROS, superoxide dismutase, hydrogen peroxide, malondialdehyde, glutathione, simultaneously reduce catalase and glutathione peroxidase levels, and upregulate HO-1, SOD-1, CAT, NQO1, GCLM mRNA levels and HO-1, SOD-1 protein levels. Additionally, Cu could observably increase the number of autophagosomes, acidic vesicle organelles (AVOs) and LC3 puncta; upregulate mRNA levels of mTOR, Beclin-1, ATG7, ATG5, ATG3, LC3II and protein levels of Beclin-1, LC3II/LC3I, downregulate LC3I mRNA level. Both treatments with BHA and ZnPP could significantly alleviate the changes of antioxidant indexes levels and ROS accumulation, reduce the increase of the number of autophagosomes, AVOs and LC3 puncta, and mitigate the above changed oxidative stress and autophagy related mRNA and protein levels induced by Cu. In summary, our findings indicated that excessive Cu could induce oxidative stress and autophagy by activating the ROS/HO-1/NQO1 pathway, and inhibition of HO-1 might attenuate Cu-induced oxidative stress and autophagy in duck renal tubular epithelial cells.