Acute Lung Injury (ALI) is a critical medical condition that induces the injury into the lung tissue, resulting in decreased the oxygen levels in the circulation and finally causes the respiratory failure. In this study, we try to made effort for scrutinized the preventive effect of gossypin against lipopolysaccharide (LPS) induced lung inflammation and explore the underlying mechanism. LPS (7.5 mg/kg) was used for induction the lung inflammation in the rats and rats were received the oral administration of gossypin (5, 10 and 15 mg/kg). The wet to dry weight lung ratio and lung index were estimated. The bronchoalveolar lavage fluid (BALF) were collected to determination the inflammatory cells, total protein, macrophages and neutrophils. ELISA kits were used for the estimation of antioxidant, inflammatory cytokines, inflammatory parameters, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) parameters. Finally, we used the lung tissue for scrutinize the alteration in the lung histopathology. Gossypin treatment significantly (p < .001) reduced the W/D ratio of lung tissue and lung index. Gossypin significantly (p < .001) decreased the total cells, neutrophils, macrophages and total protein in BALF. It is also altered the level of inflammatory cytokines, antioxidant and inflammatory parameters, respectively. Gossypin improved the level of Nrf2 and HO-1 at dose dependent manner. Gossypin treatment remarkably enhance the ALI severity via balancing the structural integrity of lung tissue, decrease the thickness of the alveolar wall, decline the pulmonary interstitial edema, and number of inflammatory cells in the lung tissue. Gossypin is a promising agent for the treatment of LPS induced lung inflammation via altering Nrf2/HO-1 and NF-κB.

Background: The investigating of study was expected to the lipid composition of diabetes and alcoholic diabetes in plasma and erythrocyte membrane biochemical profile in rats. Diabetic male Wistar Streptozotocin (STZ)-induced rats were used experimental models. Control rats (C) were maintained group I, received glucose (i.e., caloric equivalent), diabetic induced rats (STZ) group II, and group III alcoholic treated and IV diabetic and alcoholic treated rats which received 20 % (v/v) alcohol in water, administered through stomach tube (5 g/kg body weight/day). Results: STZ-induced diabetic hepatic damage in rats was observed which leads to the increased plasma lipid peroxidation, nitrate and nitrite levels. Diabetic and administration alcohol rats also suggestively lesser the activities of antioxidants, glutathione peroxidase, glutathione S-transferase, superoxide dismutase, catalase and reduced glutathione when related with control rats (group I). Plasma enzymes are normal levels and renovate the enzymic and non-enzymatic antioxidants level in experimental groups. Conclusion: The present data point out that the nitric oxide scavenging levels increased and may possibly protect and adjacent to oxidative stress and free radicals in diabetic hepatopathy rats and histopathological studies were identified in regular hepatic cortex of Group II, III and IV of animals with diabetes, alcoholic and alcohol-induced diabetes rats. (c) 2022 Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Cancer development is a sequential process as a result of various cellular adaptation events. Oral cancer (squamous cell carcinoma) is the most predominant variety of head and neck cancer. Betanin (BTN) is isolated from beetroot extracts and is a highly bioavailable antioxidant. BTN exerts a chemopreventive and cytotoxic activity on numerous cancer cells. However, precise identification of the molecules responsible for this tumor-inhibitory effect is pending. This study aimed to understand the molecular mechanisms underlying the chemopreventive effects of BTN in 7,12-dimethylbenz (a) anthracene (DMBA)-induced oral cancer in experimental hamsters. Materials and Methods: The interactions of BTN with antioxidant enzymes, lipid peroxidation, apoptosis, and inflammatory markers in the presence of DMBA were investigated in male golden Syrian hamsters. Results: Oral supplementation of BTN treatment (50 mg/kg BW) daily to oral tumor-bearing rats successfully prevented DMBA-induced oral carcinogenesis. Furthermore, BTN administration significantly prevented weight loss and reduced the tumor occurrence, burden, volume, and biochemical parameters such as TBARS, LOOH, SOD, CAT, GPx, GSH, and vitamins E and C. The histological analysis and expression pattern of molecular markers (increased apoptosis (caspase-3 and 9), proliferative markers (PCNA and Cyclin-D1), and inflammatory markers (TNF-alpha and COX-2) investigated in hamsters' buccal mucosa tissues revealed a significant anti-tumorigenic nature of BTN. Conclusion: The findings of this study show that BTN markedly reduces DMBA-induced oral cancer in hamsters.

Acute lung injury (ALI) is a common respiratory disease characterized by the alveolar edema and pulmonary inflammation, which results in the respiratory failure and even death. The current research study was planned to assess the beneficial properties of rubusoside against the LPS-provoked ALI in mice through the alleviation of oxidative stress and inflammatory responses. The viability of lipopolysaccharide (LPS)-provoked RAW 264.7 cells were assessed by MTT assay. The ALI was initiated to the mice via administering the LPS (5 mg/kg) for 3 days and supplemented with the 30 mg/kg of rubusoside. The lung edema, total cells, and protein content were assessed by standard methods. The pro-inflammatory markers level was investigated by assay kits and the antioxidant biomarkers were analyzed by standard techniques. The levels of inflammatory biomarkers in the LPS-provoked RAW 264.7 cells and lung tissues of ALI mice were studied by RT-PCR assay. The lung tissues were analyzed microscopically to identify the histological alterations. The rubusoside treatment effectively decreased the RAW 264.7 cells viability. The rubusoside also inhibited the lung edema, IL-6, and TNF-α content, ROS accumulation, and TBARS level in the LPS-challenged ALI mice. Rubusoside also improved the GSH content and CAT activity in the ALI mice. The levels of TLR-4, COX-2, iNOS, and IL-1β were effectively down-regulated by the rubusoside in both LPS-challenged RAW 264.7 cells and lung tissues. The finding of lung tissue histopathology was also proved the therapeutic action of rubusoside. Altogether, our results suggest that rubusoside demonstrates therapeutic property against the LPS-challenged ALI in mice via inhibiting the inflammatory responses and it can be an effective drug to treat the ALI in future.

BACKGROUND:Background: Acute lung injury (ALI) is one kind of frequently occurred emergency in Intensive Care Unite with a high mortality. The underlying causes are uncontrolled inflammatory reactions and intractable hypoxemia, which are difficult to control and improve. In the past 10 years, gas medical studies have found that both hydrogen molecules and oxygen molecules have protective effects on acute lung injury by improving inflammatory reactions and hypoxia, respectively. Oxygen is an oxidant and hydrogen is an antioxidant. In this study, we investigated the combined effect of above two-gas molecular on lipopolysaccharide (LPS) -induced acute lung injury.METHODS:To clarify whether the combination of hydrogen and oxygen could increase or cancel out the protective effect, an ALI mice model induced by intraperitoneal injection of LPS was established, and the degree of lung tissue and mitochondria damage was evaluated based on the pathological sections, inflammatory factors, wet-dry ratio, bronchoalveolar lavage fluid (BALF). Immunohistochemistry, electron microscopy, western blotting and other detection methods also used to evaluate the therapeutic effect on acute lung injury model.RESULTS:We observed that the combined protective effect of hydrogen and oxygen was superior to their respective protective effects, and the specific molecular mechanisms of the two therapies might be different.CONCLUSION:Hydrogen plays a more important role in the inflammatory and anti-apoptosis mechanisms, while oxygen improves hypoxia of the body, and thus, its molecular mechanism may be closely associated to the hypoxia pathways.

The stress response can be triggered during the perioperative period by tension, fear, anesthesia, surgical trauma, and various postoperative adverse stimuli, leading to significant changes in the endocrine, metabolic, and immune systems of patients. In particular, immunosuppression induced by the stress response has adverse effects on the postoperative recovery of patients. As acupuncture stimulation-related technologies have been rapidly developed and applied in recent years, a number of basic and clinical studies have confirmed that acupoint stimulation can regulate the immune system via local, neurological, and endocrine pathways. Moreover, acupoint stimulation treatment has also been shown to reduce the adverse effects of immunosuppression by affecting the release of various cytokines, such as interleukin (IL) 1, IL-2, IL-4, IL-6, IL-10, IFN-γ, and tumor necrosis factor (TNF) β, immunoglobulins, complement proteins, and T cell markers such as CD3, CD4, and CD4/CD8 via the regulation of macrophages, neutrophils, NK cells, and endogenous opioids. In addition, acupuncture stimulation treatment during the perioperative period can also significantly decrease the amount of anesthetic required for anesthesia, effectively reduce nausea and vomiting, relieve post-operative pain, and accelerate the recovery of physiological functions. Therefore, acupuncture stimulation treatment has shown important potential for clinical applications.

Pneumonia is a chronic disorder of the respiratory system associated with worsening quality of life and a significant economic burden. Pinitol, a plant cyclic polyol, has been documented for immune‐inflammatory potential. The aim of present investigation was to evaluate the potential and possible mechanism of action of pinitol against lipopolysaccharide (LPS)‐induced pneumonia in the experimental animal model. Pneumonia was induced in Sprague‐Dawley rats by intratracheal administration of LPS (2 mg/kg). Animals were treated with either vehicle or dexamethasone or pinitol (5 or 10 or 20 mg/kg). Potential of pinitol against LPS‐induced pulmonary insult was assessed based on behavioral, biochemical, molecular, and ultrastructural studies. Intratracheal instillation of LPS induced significant (P < .05) inflammatory infiltration in bronchoalveolar lavage fluid (BALF) and lung tissue reflected by elevated pleural effusion volume, lung edema, BALF polymorphonuclear leukocytes count and lung myeloperoxidase levels, which was attenuated by pinitol (10 and 20 mg/kg) administration. Pinitol also markedly (P < .05) inhibited LPS‐induced alterations in electrocardiographic, hemodynamic changes, right ventricular, and lung function tests. The LPS‐induced downregulated nuclear factor erythroid 2–related factor 2 (Nrf‐2) and heme oxygenase‐1 (HO‐1), whereas upregulated transforming growth factor‐β (TGF‐β), tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), IL‐6, NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3), and inducible nitric oxide synthase (iNOs) lung messenger RNA expressions were significantly (P < .05) inhibited by pinitol. Western blot analysis suggested pinitol markedly (P < .05) decreased nuclear factor‐κB (NF‐κB), inhibitor of nuclear factor κB (IkBα), toll‐like receptor 4 (TLR‐4), and cyclooxygenase‐II (COX‐II) protein expressions in the lung. These findings were further supported by histological and ultrastructural analyses of lung tissue that show pinitol significantly (P < .05) ameliorates LPS‐induced aberrations in lung tissue. In conclusion, pinitol attenuated LPS‐induced pneumonia via inhibition of TLR‐4 to downregulate the NF‐κB/IκBα signaling cascade and thus ameliorated the production of proinflammatory cytokines (TNF‐α, ILs, NLRP3, and TGF‐β), inflammatory mediators (COX‐II and iNOs) and elevated oxidative stress (Nrf‐2 and HO‐1).

Hyperlipidemia is associated with metabolic disorders, but the detailed mechanisms and related interventions remain largely unclear. As a functional food in Asian diets, Herba houttuyniae has been reported to have beneficial effects on health. The present research was to investigate the protective effects of Herba houttuyniae aqueous extract (HAE) on hyperlipidemia-induced liver and heart impairments and its potential mechanisms. Male C57BL/6J mice were administered with 200 or 400 mg/kg/day HAE for 9 days, followed by intraperitoneal injection with 0.5 g/kg poloxamer 407 to induce acute hyperlipidemia. HAE treatment significantly attenuated excessive serum lipids and tissue damage markers, prevented hepatic lipid deposition, improved cardiac remodeling, and ameliorated hepatic and cardiac oxidative stress induced by hyperlipidemia. More importantly, NF-E2 related factor (Nrf2)-mediated antioxidant and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathways as well as mitochondrial complex activities were downregulated in the hyperlipidemic mouse livers and hearts, which may be attributable to the loss of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity: all of these changes were reversed by HAE supplementation. Our findings link the AMPK/PGC-1α/Nrf2 cascade to hyperlipidemia-induced liver and heart impairments and demonstrate the protective effect of HAE as an AMPK activator in the prevention of hyperlipidemia-related diseases.

Pneumonia is a chronic disorder of the respiratory system associated with worsening quality of life and a significant economic burden. Pinitol, a plant cyclic polyol, has been documented for immune-inflammatory potential. The aim of present investigation was to evaluate the potential and possible mechanism of action of pinitol against lipopolysaccharide (LPS)-induced pneumonia in the experimental animal model. Pneumonia was induced in Sprague-Dawley rats by intratracheal administration of LPS (2 mg/kg). Animals were treated with either vehicle or dexamethasone or pinitol (5 or 10 or 20 mg/kg). Potential of pinitol against LPS-induced pulmonary insult was assessed based on behavioral, biochemical, molecular, and ultrastructural studies. Intratracheal instillation of LPS induced significant (P < .05) inflammatory infiltration in bronchoalveolar lavage fluid (BALF) and lung tissue reflected by elevated pleural effusion volume, lung edema, BALF polymorphonuclear leukocytes count and lung myeloperoxidase levels, which was attenuated by pinitol (10 and 20 mg/kg) administration. Pinitol also markedly (P < .05) inhibited LPS-induced alterations in electrocardiographic, hemodynamic changes, right ventricular, and lung function tests. The LPS-induced downregulated nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1), whereas upregulated transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), and inducible nitric oxide synthase (iNOs) lung messenger RNA expressions were significantly (P < .05) inhibited by pinitol. Western blot analysis suggested pinitol markedly (P < .05) decreased nuclear factor-κB (NF-κB), inhibitor of nuclear factor κB (IkBα), toll-like receptor 4 (TLR-4), and cyclooxygenase-II (COX-II) protein expressions in the lung. These findings were further supported by histological and ultrastructural analyses of lung tissue that show pinitol significantly (P < .05) ameliorates LPS-induced aberrations in lung tissue. In conclusion, pinitol attenuated LPS-induced pneumonia via inhibition of TLR-4 to downregulate the NF-κB/IκBα signaling cascade and thus ameliorated the production of proinflammatory cytokines (TNF-α, ILs, NLRP3, and TGF-β), inflammatory mediators (COX-II and iNOs) and elevated oxidative stress (Nrf-2 and HO-1).

Background: Hemorrhagic shock could induce acute lung injury (ALI), which is associated with cell hypoxia, lung tissue inflammation, free radical damage, and excessive cell apoptosis. Our previous studies demonstrated that hyperoxygenated solution could alleviate cell hypoxia. Furthermore, hydrogen-rich solution (HS) could relieve lung tissue inflammation, free radical damage and excessive cell apoptosis. Therefore we hypothesize that Hyperoxygenated Hydrogen-rich solution (HOHS) can protect the lung against ALI. Materials and methods: SD rats were randomly divided into five groups (n = 6 at each time point in each group) and were exposed to Hemorrhagic shock induced ALI, and then treated with lactated Ringer's solution (LRS), hyperoxygenated solution, HS, and HOHS, respectively. The protective effects of these solutions were assessed using methods as follows: arterial blood samples were collected for blood gas analysis; Bronchoalveolar lavage fluid was collected for cell count and protein quantification; lung tissue samples were collected to measure wet/dry ratio, as well as levels of T-SOD, MDA, TNF-alpha, and IL-6; Caspase-3 and TUNEL-positive cells, and pathological changes were observed under light microscope; ALI was scored using the Smith scoring method; ultrastructural changes of lung tissues were further observed with transmission electron microscopy. Results: The results indicated that PaO2, PaCO2, and T-SOD increased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group; and conversely that the levels of lactate, MDA, TNF-alpha and IL-6, cell count, protein content, caspase-3 and TUNEL-positive cells as well as ALI score decreased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group. Morphological observation with optical microscope and electron microscopy showed that compared with the LRS group, cell damage in the three treatment groups improved to a varying extent, especially evident in the HOHS group. Conclusions: These findings demonstrate that HOHS can protect the lung against ALI induced by hemorrhagic shock. (C) 2019 Elsevier Inc. All rights reserved.

Objective To evaluate the effects of hydrogen-rich saline on liver injury in a rat model of hemorrhagic shock and resuscitation.Methods Forty-eight pathogen-free male Sprague-Dawley rats,aged 6-8 weeks,weighing 150-250 g,were randomly divided into 3 groups (n =16 each) using a random number table:sham operation group (group Sham),hemorrhagic shock and resuscitation group (group HR),and hydrogen-rich saline group (group HRS).Severe hemorrhagic shock was induced according to the method described by Wiggers.Lactated Ringer's solution and hydrogen-rich saline were given for resuscitation in HR and HRS groups,respectively.At 6 h after resuscitation,blood samples were collected from the femoral artery for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations by automatic biochemical analyzer.The rats were then sacrificed,and liver specimens were obtained for examination of histopathological changes (using light microscope) and for determination of total superoxide dismutase (T-SOD) activity,malondialdehyde (MDA) content,and tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations (using the corresponding kits).Results Compared with group Sham,the levels of ALT and AST in serum and IL-6,TNF-α,T-SOD and MDA in liver tissues were significantly increased in HR and HRS groups (P＜0.01).Compared with group HR,the levels of ALT and AST in serum and IL-6,TNF-α,and MDA in liver tissues were significantly decreased,and the T-SOD level was significantly increased in group HRS (P＜0.01).The histopathological changes of livers were significantly attenuated in group HRS as compared with group HR.Conclusion Hydrogen-rich saline can reduce liver injury in a rat model of hemorrhagic shock and resuscitation.

Muscle atrophy occurs in several pathologic conditions such as diabetes and chronic obstructive pulmonary disease (COPD), as well as after long-term clinical administration of synthesized glucocorticoid, where increased circulating glucocorticoid accounts for the pathogenesis of muscle atrophy. Others and we previously reported mitochondrial dysfunction in muscle atrophy-related conditions and that mitochondria-targeting nutrients efficiently prevent kinds of muscle atrophy. However, whether and how mitochondrial dysfunction involves glucocorticoid-induced muscle atrophy remains unclear. Therefore, in the present study, we measured mitochondrial function in dexamethasone-induced muscle atrophy in vivo and in vitro, and we found that mitochondrial respiration was compromised on the 3rd day following after dexamethasone administration, earlier than the increases of MuRF1 and Fbx32, and dexamethasone-induced loss of mitochondrial components and key mitochondrial dynamics proteins. Furthermore, dexamethasone treatment caused intracellular ATP deprivation and robust AMPK activation, which further activated the FOXO3/Atrogenes pathway. By directly impairing mitochondrial respiration, FCCP leads to similar readouts in C2C12 myotubes as dexamethasone does. On the contrary, resveratrol, a mitochondrial nutrient, efficiently reversed dexamethasone-induced mitochondrial dysfunction and muscle atrophy in both C2C12 myotubes and mice, by improving mitochondrial function and blocking AMPK/FOXO3 signaling. These results indicate that mitochondrial dysfunction acts as a central role in dexamethasone-induced skeletal muscle atrophy and that nutrients or drugs targeting mitochondria might be beneficial in preventing or curing muscle atrophy.