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Skin injuries can have unexpected surfaces, leading to uneven wound surfaces and inadequate dressing contact with these irregular surfaces. This can decrease the dressing's haemostatic action and increase the healing period. This study recommends the use of sticky and flexible cryogel coverings to promote faster haemostasis and efficiently handle uneven skin wounds. Alginate cryogels have a fast haemostatic effect and shape flexibility due to their macroporous structure. The material demonstrates potent antibacterial characteristics and enhances skin adherence by adding grafted chitosan with gallic acid. In irregular defect wound models, cryogels can cling closely to uneven damage surfaces due to their amorphous nature. Furthermore, their macroporous structure allows for quick haemostasis by quickly absorbing blood and wound exudate. After giving the dressing a thorough rinse, its adhesive strength reduces and it is simple to remove without causing any damage to the wound. Cryogel demonstrated faster haemostasis than gauze in a wound model on a rat tail, indicating that it has considerable potential for use as a wound dressing in the biomedical area. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. Patient concerns: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. Diagnosis: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). Interventions: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. Outcomes: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. Conclusion: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation. [ABSTRACT FROM AUTHOR]

Background and objectives: The molecular mechanisms mediating external root resorption are poorly understood. Interleukin‐33 (IL‐33) expression increased remarkably in the periodontal ligament (PDL) under orthodontic loading. The IL‐33‐driven responses are delicately cell type‐ and tissue context‐dependent. It is unknown how IL‐33 act on osteoclastogenesis in the context of root surface. This study aimed to investigate the effect of IL‐33 on osteoclastogenesis in the PDL under mechanical loading. Materials and Methods: C57BL/6J mice were treated with injections of phosphate buffer saline (PBS) or recombinant mouse IL‐33 (rmIL‐33, 6 μl, 30 μg/ml), and subjected to models of orthodontic tooth movement. Tartrated resistant acid phosphates (TRAP)‐positive cells and IL‐33 expressions were examined in the PDL. IL‐33 release from human PDL cells (hPDLCs) was detected by ELISA. Cementoblast‐like (OCCM‐30) cells were cultured in the presence of rmIL‐33 to examine the release of osteoclast‐regulatory proteins. The effects of rmIL‐33 on osteoclastogenesis were examined in vitro in cultures of bone marrow macrophages (BMMs) and in BMMs‐OCCM‐30 cocultures. Expressions of osteoclast‐specific or ‐related genes and proteins were investigated in BMMs‐OCCM‐30 cocultures treated with or without rmIL‐33, in the presence or absence of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) neutralizing antibody. Results: Interleukin‐33 expressions were upregulated in the PDL under orthodontic loading. Static compressive force enhanced expression and release of IL‐33 from hPDLCs. Administration of rmIL‐33 resulted in reduced number of TRAP‐positive cells in the PDL, and inhibited osteoclast differentiation from BMMs in vitro. OCCM‐30 cells had varied osteoprotegerin (OPG) / receptor activator for nuclear factor‐κB ligand (RANKL) secretion and increased release of GM‐CSF under rmIL‐33 stimulation. Treatment with rmIL‐33 in BMMs‐OCCM‐30 cocultures resulted in inhibited differentiation and decreased activity of osteoclasts, and these effects were partially reversed by GM‐CSF neutralizing antibody. Conclusions: Interleukin‐33 inhibits osteoclastogenesis in the PDL under orthodontic loading. The anti‐osteoclastogenic effects were mediated partly by directly affecting osteoclast precursors and partly by cementoblast‐mediated release of GM‐CSF. [ABSTRACT FROM AUTHOR]

Abstract: Our previous study has revealed that malonyl-ginsenosides from Panax ginseng (PG-MGR) play a crucial role in the treatment of T2DM. However, its potential mechanism was still unclear. In this study, we investigated the anti-diabetic mechanisms of action of PG-MGR in high fat diet-fed (HFD) and streptozotocin-induced diabetic mice and determined the main constituents of PG-MGR responsible for its anti-diabetic effects. Our results showed that 16 malonyl ginsenosides were identified in PG-MGR by HPLC-ESI-MS/MS. PG-MGR treatment significantly reduced fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels and improved insulin resistance and glucose tolerance. Simultaneously, PG-MGR treatment improved liver injury by decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) expression. Furthermore, Western blot analysis demonstrated that the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, p-AMPK/AMPK, p-ACC/ACC and GLUT4 in liver and skeletal muscle were significantly up-regulated after PG-MGR treatment, and the protein expression levels of p-IRS-1/IRS-1, Fas and SREBP-1c were significantly reduced. These findings revealed that PG-MGR has the potential to improve glucose and lipid metabolism and insulin resistance by activating the IRS-1/PI3K/AKT and AMPK signal pathways. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is not well understood. Experimental data from numerous investigations support the idea that aberrant activity of D1 dopamine receptor-positive medium spiny neurons in the striatal direct pathway is associated with LID. However, a direct link between the real-time activity of these striatal neurons and dyskinetic symptoms remains to be established. Methods: We examined the effect of acute levodopa treatment on striatal c-Fos expression in LID using D1-Cre PD rats with dyskinetic symptoms induced by chronic levodopa administration. We studied the real-time dynamics of striatal D1+ neurons during dyskinetic behavior using GCaMP6-based in vivo fiber photometry. We also examined the effects of striatal D1+ neuronal deactivation on dyskinesia in LID rats using optogenetics and chemogenetic methods. Results: Striatal D1+ neurons in LID rats showed increased expression of c-Fos, a widely used marker for neuronal activation, following levodopa injection. Fiber photometry revealed synchronized overactivity of striatal D1+ neurons during dyskinetic behavior in LID rats following levodopa administration. Consistent with these observations, optogenetic deactivation of striatal D1+ neurons was sufficient to inhibit most of the dyskinetic behaviors of LID animals. Moreover, chemogenetic inhibition of striatal D1+ neurons delayed the onset of dyskinetic behavior after levodopa administration. Conclusion: Our data demonstrated that aberrant activity of striatal D1+ neuronal population was causally linked with real-time dyskinetic symptoms in LID rats. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of San-Ao Decoction (三拗汤, SAD) on water metabolism of bronchial asthra model mice. Methods: Forty-five female BALB/c mice were randomly divided into control, model and SAD groups by a random number table, 15 mice in each group. A composite method with ovalbumin (OVA) sensitization and challenge was developed to establish bronchial asthma model. Mice in the control group were intraperitoneally injected with distilled water without aerosol inhalation challenge. On day 15–22, 0.3 mL SAD was administered via gastric route in SAD group, one time per day, while an equivalent volume of normal saline was used for gastric administration in the control and model groups. Changes in airway resistance in the inspiratory phase (RI-R-Area) were detected using an AniRes2005 system, and 5-h urine output was collected by metabolic cages. Histopathological changes in lung and kidney were observed by hematoxylin-eosin staining. mRNA expressions of aquaporin (AQP) 1 and AQP2 in kidney were detected by reverse transcription-polymerase chain reaction, and the protein expressions of AQP1 and AQP2 in kidney were detected by immunohistochemistry. Enzyme-linked immune sorbent assay was used to detect the OVA-specific endothelium-1 (ET-1), antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), prostaglandin E2 (PGE2), and angiotensin II (Ang II) levels in serum, lung and kidney tissues, respectively. The nitric oxide (NO) contents in serum, lung, and kidney tissues were tested by chemical method, respectively. Results: Compared with the control group, the serum IgE level in model group increased (P<0.01). Following the pathologic changes in lung tissue, no significant change in kidney tissue was observed among 3 groups. Compared with the control group, the mice in the model group showed elevated airway resistance during inhalation phase, higher mRNA and protein expression levels on AQP1 and AQP2 in kidney tissue and higher ET-1 levels in serum, lung and kidney tissues, ADH and ANP in lung and serum, PGE2 in kidney, Ang II in lung and kidney tissues (P<0.05 or P<0.01), but decreased in 5-h urinary output as well as NO and PGE2 contents in serum and lung tissues (P<0.05 or P<0.01). Compared with the model group, the mice in the SAD group showed a weakened airway resistance in inspiratory phase, lower mRNA and protein expressions of AQP1 and AQP2 in kidney tissues, lower levels of ET-1, ADH, ANP in serum as well as ET-1, ANP, Ang II levels in kidney tissues (P<0.05 or P<0.01), whereas 5-h urinary output, NO content in kidney, ADH, ANP and PGE2 levels in lung and Ang II in serum increased (P<0.05 or P<0.01). Conclusion: San-Ao Decoction can regulate the urine volume through regulating AQP1 and AQP2 expression, and the expression of these in the kidneys might be regulated by ET-1, NO and Ang II. [ABSTRACT FROM AUTHOR]

Wound healing can be divided into different phases, and timely initiation and cessation of these stages is key to successful wound healing; otherwise, scar tissue forms in the wounded area. Connexins (Cxs) were confirmed to influence scar formation, and Cx43, an indispensable member of the Cx family, was shown to be involved in this process. Our study investigated the regulatory role of Cx43 in scar formation and the possible cell signalling pathways. We established oral mucosa and skin wound healing models in C57BL/6J mice. RT‐PCR, western blotting, immunohistochemistry and immunofluorescence were used to examine the expression of ECM components and key proteins in cell signalling pathways (TGF‐β1, Smad2/3, Cx43, Erk1/2 MMP‐1 and collagen III). After injury, buccal mucosa wounds healed with no scar, whereas skin wounds healed with an evident scar. Nevertheless, TGF‐β1 expression gradually increased by the 5th day after injury; Cx43 expression showed a similar response, with a progressive increase in the skin and a peak on day 14. In contrast, TGF‐β1 and Cx43 expression in the oral mucosa remained low. The high level of TGF‐β1 increased p‐Smad2/3 levels and then induced Cx43, whereas increased expression of Cx43 antagonised the phosphorylation of Erk1/2, a protein downstream of Cx43, which affected MMP‐1 synthesis. MMP‐1 deficiency led to collagen III accumulation and facilitated scar formation. We demonstrated that TGF‐β1‐induced Cx43 promotes scar formation via the Erk/MMP‐1/collagen III pathway. [ABSTRACT FROM AUTHOR]

Background: A key cause of the high mortality of cardiovascular diseases is the cardiomyocyte inability to renew after cardiac injury. As a promising strategy to supplement functional myocytes for cardiac repair, there is a pressing need to understand the cellular and molecular mechanisms of heart regeneration.Methods: Seven genetic mouse lines were used: global OSM (oncostatin M) knockout, monocyte-/macrophage-specific OSM deletion, cardiomyocyte-specific lines, including OSM receptor deletion, gp130 (glycoprotein 130) deletion, gp130 activation, and Yap (yes-associated protein) ablation with gp130 activation mice. A series of molecular signaling experiments, including RNA sequencing, immunostaining, coimmunoprecipitation, and imaging flow cytometry, were conducted. Two models of cardiac injury, apical resection and myocardial infarction operation, were performed in neonatal, juvenile, and adult mice. Heart regeneration and cardiac function were evaluated by Masson staining and echocardiography, respectively. Gene recombinant adenovirus-associated virus was constructed and infected myocardial-infarcted mice as a gene therapy.Results: OSM was identified by RNA sequencing as a key upstream regulator of cardiomyocyte proliferation during neonatal heart regeneration in mice. Cardiomyocyte proliferation and heart regeneration were suspended in neonatal mice after cardiac injury when OSM was conditionally knockout in macrophages. The cardiomyocyte-specific deficiency of the OSM receptor heterodimers, OSM receptor and gp130, individually in cardiomyocytes reduced myocyte proliferation and neonatal heart regeneration. Conditional activation of gp130 in cardiomyocytes promoted cardiomyocyte proliferation and heart regeneration in juvenile and adult mice. Using RNA sequencing and functional screening, we found that Src mediated gp130-triggered cardiomyocyte proliferation by activating Yap (yes-associated protein) with Y357 phosphorylation independently of the Hippo pathway. Cardiomyocyte-specific deletion of Yap in Myh6-gp130ACT mice blocked the effect of gp130 activation-induced heart regeneration in juvenile mice. Gene therapy with adenovirus-associated virus encoding constitutively activated gp130 promoted cardiomyocyte proliferation and heart regeneration in adult mice after myocardial infarction.Conclusions: Macrophage recruitment is essential for heart regeneration through the secretion of OSM, which promotes cardiomyocyte proliferation. As the coreceptor of OSM, gp130 activation is sufficient to promote cardiomyocyte proliferation by activating Yap through Src during heart regeneration. gp130 is a potential therapeutic target to improve heart regeneration after cardiac injury. [ABSTRACT FROM AUTHOR]

Objective. To establish a porcine eye model for manual sub-Bowman layer photorefractive keratomileusis (SBPRK), which is a reformed surface ablation refractive surgery that results in preserving the corneal Bowman layer (BL). Methods. The SBPRK group consisted of eleven eyes of 8 healthy pigs with BL flaps by mechanical technique followed by laser ablation. Regarding the remaining 5 eyes, 3 random eyes had transepithelium photorefractive keratectomy (TransPRK) (the TransPRK group), while the other 2 eyes were untreated (the blank control group). All the pigs were followed up for 8 weeks. Slit-lamp biomicroscopy and optical coherence tomography (OCT) were examined before the surgeries and at 1 week, 4 weeks, and 8 weeks after the surgeries. Results. In a few days after the surgery, 3 eyes of the SBPRK group were excluded from the study because of poor healing of the corneal flaps. At the 1st postoperative week, one eye had an irregular defect of about 3 mm in the central corneal epithelium area; the cornea of the other 7 eyes had just light edema with intact epithelium just like the cornea of the TransPRK group. At the 4th week, in the SBPRK group, the cornea was slightly hazy (haze stage 1). While in the TransPRK group, the cornea was hazier (haze stage 2). At the 8th week, in the SBPRK group, both corneas were almost transparent, and the edges of the BL flaps could not be clearly seen. Meanwhile, in the TransPRK group, the corneal haze became lighter and thinner. OCT showed that, in the SBPRK group, there was high reflection in the BL layer, and it was obvious at 1 week postoperation, decreased at 4 weeks, and calmed down at 8 weeks. However, in the TransPRK group, the high reflection diffused in the anterior corneal stroma at 1 week postoperation, enhanced at 4 weeks, and weakened at 8 weeks. Conclusions. Preserving the BL while conducting surface refractive surgery may result in less haze than TransPRK. However, further study is still needed, and this technique still requires refining until it becomes a standard clinical procedure. [ABSTRACT FROM AUTHOR]

Paraquat (PQ) poisoning can cause oxidative stress, acute lung injury (ALI), and fibrosis. Excess oxidative stress can induce mitophagy. However, whether PQ exposure can induce mitophagy, contributing to the development of ALI and pulmonary fibrosis in vivo has not been clarified. Here, we show that PQ exposure induces ALI and fiber accumulation in the lung of rats in a time-dependent manner, accompanied by upregulating fibronectin (FN) and Collagen I (COL-I) expression. PQ exposure increased mitophagosome formation and PINK1 and Parkin expression in the lungs of rats. Similarly, PQ exposure reduced the viability and mitochondrial membrane potential, but enhanced FN, COL-I, PINK1, and Parkin expression in A549 cells. In contrast, PINK1 silencing significantly mitigated the PQ-upregulated Parkin, FN, and COL-I expression in A549 cells. Hence, PQ exposure induced ALI and fibrosis in rats by enhancing the PINK1/Parkin signaling and profibrotic factor expression in the lungs. Therefore, our findings suggest that the PINK1/Parkin signaling may be new therapeutic targets and may provide new insights in the pathogenesis of PQ-related ALI in rats. [ABSTRACT FROM AUTHOR]

Purpose: The roles of commensal bacteria after intestinal ischemia and reperfusion (IIR) are unclear. In current study, we aim to investigate the effects and underlying mechanisms of commensal bacteria in injury and epithelial restitution after IIR.Methods: Commensal gut bacteria were deleted by broad-spectrum antibiotics in mice. IIR was induced by clamping superior mesenteric artery. Intestinal injury, permeability, epithelial proliferation, and proinflammatory activity of mesenteric lymph were investigated.Results: Commensals deletion improved mice survival in the early phase, but failed to improve the overall survival at 96 h after IIR. Commensals deletion reduced proliferation of intestinal epithelial cells (IEC) and augmented proinflammatory activity of mesenteric lymph after IIR. Lipopolysaccharides (LPS) supplement promoted IEC proliferation and improved survival in mice with commensals deletion after IIR. LPS induced production of prostaglandin E2 (PGE2) in mucosa via toll-like receptor 4-NFκB-cyclooxygenase 2 pathway. PGE2 enhanced IEC proliferation in vivo, which was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2. Blocking of EGFR, PI3K/Akt activity abolished LPS-induced IEC proliferation.Conclusions: Commensal bacteria are essential for epithelial restitution after IIR, which enhance IEC proliferation via induction of PGE2. [ABSTRACT FROM AUTHOR]

As the initial part in the development of osteoarthritis (OA), subchondral bone sclerosis has been considered to be initiated by excess mechanical loading and proven to be correlated to other pathological changes. Sclerostin, which is an essential mechanical stress response protein, is encoded by the SOST gene. It is expressed in osteocytes and mature chondrocytes and has been proven to be closely correlated to OA. However, the relationship and mechanism between the SOST gene and the development of OA remain unclear. The aim of the present study was to investigate the role of the SOST gene in OA pathogenesis in the subchondral bone. A knee anterior cruciate ligament transection (ACLT) mouse osteoarthritis (OA) model on SOST-knockout (SOST KO) and wild-type (WT) mice was established. The pathogenic and phenotypic changes in the subchondral bone were investigated by histology, micro-CT, immunohistochemistry, TRAP staining, Masson staining, and Toluidine blue staining. It was found that sclerostin expression decreased in both the calcified cartilage and mineralized subchondral structures during the development of OA. Joint instability induced a severe cartilage degradation phenotype, with higher OARSI scores in SOST KO mice, when compared to WT mice. SOST KO mice with OA exhibited a higher BMD and BV/TV ratio, as well as a higher rate of bone remodeling and TRAP-positive cell number, when compared to the WT counterparts, but the difference was not significant between the sham-operation groups. It was concluded that loss of sclerostin aggravates knee OA in mice by promoting subchondral bone sclerosis and increasing catabolic activity of cartilage. [ABSTRACT FROM AUTHOR]

The 4 properties of Chinese materia medica refer to cold, hot, warm, and cool. In the present study, the effects of the Coptis, the prepared aconite root, and dried ginger rhizome were compared with regard to the rectal and skin temperature changes of the related body surface acupuncture points (Dazhui, Zhiyang, Mingmen, Zhongwan, and Shenque). The investigation aimed to explore the thermal sensitive points, which can reflect the cold and hot properties of the Chinese herbs. This study showed that the prepared aconite root and dried ginger rhizome exhibited a warming effect on the body temperature, whereas the warming sensitive points were Zhongwan, Shenque, Dazhui, and Zhiyang. Coptis exhibited both a warming and a cooling effect on the body temperature, and the cooling sensitive point was Dazhui. The concomitant effect of these three Chinese herbs on the regulation of the body temperature was reflected by Dazhui. However, there are still some limitations and one-sidedness. For instance, the cold and hot property of some herbs cannot be fully reflected through relevant acupoints on the conception and governor vessels. More detecting sites such as ears and internal organs will be selected for further exploration of Chinese herbs’ cold and hot property. [ABSTRACT FROM AUTHOR]

Background. To investigate the specific link between lung and large intestine. Methods. Rat COPD-like model was prepared. Mirabilite or Chinese rhubarb was administrated intragastrically to stimulate the large intestine. Histological analysis of lung inflammation was assessed. The tissues levels of SP, VIP, NK1R, VIPR1, and VIPR2 were measured by using ELISA kits. In addition, mouse model of allergic asthma was prepared. Mirabilite was administrated intragastrically to stimulate the large intestine. Airway responsiveness and lung inflammation were assessed. The tissues levels of SP, VIP, NKA, NKB, NK1R, VIPR1, and VIPR2 were measured by using ELISA kits. Results. Stimulating the intestine with Mangxiao or Dahuang, SP, NK-1R, VIP, VIPR1, and VIPR2 were significantly increased in intestine tissues of rats with COPD and mice with asthma. Meanwhile, the SP and NK1R were significantly decreased, while VIP, VIPR1, and VIPR2 were significantly increased in lung tissues. An abnormal secretion of SP and VIP can be observed in other tissues; however, no marked changes were found in the receptors. The NKA and NKB levels were similar in lung tissues of mice with asthma among groups. Conclusions. Stimulating intestine with Mangxiao or Dahuang can specifically regulate the secretion of SP, VIP, and the receptors in lung tissues. [ABSTRACT FROM AUTHOR]

Objective: To investigate the synergistic anti-inflammatory effect of Radix Platycodon in combination with herbs for cleaning-heat and detoxification and its mechanism for Fei (肺)-targeting. Methods: Forty Wistar rats were randomly divided into five groups (8 per group): the sham-operated group, model group, Radix Platycodon group, Flos Lonicera and Fructus Forsythia (LF) group, and Radix Platycodon, Flos Lonicera and Fructus Forsythia combination (PLF) group, using a random number table. A rat chronic obstructive pulmonary disease (COPD) model was established by passive smoking and intratracheal instillation of lipopolysaccharide (LPS). The treatments started from the 15th day of passive smoking for a total duration of 14 days. At the end of the treatment, changes in the following measurements were determined: lung histopathology, inflammatory cytokines including tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β) and interleukin IL-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), and mRNA expression of endogenous active substance intestinal trefoil factor 3 (TFF3) in the lung tissue. Results: Light microscopy showed that compared with the sham-operated group, rats in the COPD model group had disrupted alveolar structure, collapsed local alveoli, significantly widened or even fused alveolar septa, and massive infiltration of inflammatory cells in the alveolar wall and interstitium. In addition, significant bronchial epithelium hyperplasia, partially shed epithelia, and marked inflammatory cell infiltration in the bronchial wall and its surrounding tissues were noticed. Electron microscopy showed that rats in the model group had degeneration of alveolar type II epithelial cell; reduction, breakage or even loss of cell surface microvilli; swollen mitochondria with disappearing cristae and vacuole-like structure; and, increased secondary lysosomes in alveolar macrophages. The TNF-α, TGF-β and IL-1β levels and white blood cell (WBC) count in BALF were significantly increased ( P<0.01 or P<0.05) and TFF3 mRNA expression in the lung tissue was significantly reduced ( P<0.01). After treatment, the pathological morphology of lung injury was less severe in all three treatment groups. In addition, TGF-β and IL-1β and WBC count in BALF were decreased ( P<0.01 or P<0.05), and TFF3 mRNA expression in the lung tissue was significantly increased in the PLF group ( P<0.01). Compared with the LF group, the IL-1β in BALF was significantly decreased P<0.05), and TFF3 mRNA expression was significantly increased ( P<0.05) in the PLF group. Conclusions: Radix Platycodon synergizes with herbs for cleaning-heat and detoxification in reducing inflammatory injury in a rat model of COPD. The synergistic anti-inflammatory effect is reflected in the improvement in pathological changes and in the reduction of IL-1β levels in BALF. The mechanism of such synergistic action may be related to its effect on maintaining the TFF3 mRNA expression and Fei-targeting function. [ABSTRACT FROM AUTHOR]

A new flavonoid glycoside, named aquisiflavoside, was isolated from the leaves of Aquilaria sinensis (Lour.) Gilg, and its structure was elucidated by spectroscopic analyses. Aquisiflavoside was evaluated for the inhibition of nitric oxide (NO) production induced by lipopolysaccharide in macrophage cell line RAW 264.7 and exhibited a potent inhibitory activity against NO production in a dose-dependent manner with an IC50 value of 34.95 μM. [ABSTRACT FROM AUTHOR]

Background: Pituitary adenomas are common brain tumors. Although transsphenoidal surgery are able to achieve extensive tumor removal, the rate of recurrence ranges from 5 to 20% depending on the different subtype. Further understanding of these tumors is needed to develop novel strategies to improve the prognosis of patients. But their metabolic characteristics are largely unknown.Methods: We used metabolomic, transcriptomic, and proteomic approaches to systematically investigate eight subtypes of pituitary adenomas and normal pituitary glands. By blocking IDH2, we investigate IDH2 play an inhibitory role in GH tumor cell growth and tumor secretion.Results: We found that all of the pituitary adenomas displayed downregulated glucose metabolism and glycolysis compared to normal tissues. Together with the differences in amino acids and fatty acids, we categorized these tumors into three clusters. We then re-established the reprogrammed metabolic flux in pituitary adenomas based on multiomic analyses. Take growth hormone-secreting pituitary adenomas as an example, we revealed that IDH2 is a key player in the reprogrammed metabolism of such tumors. By blocking IDH2, we confirmed that IDH2 is a potential target for the inhibition of tumor cell growth and tumor secretion.Conclusions: Our study first uncovered the metabolic landscape of pituitary adenomas and demonstrated a possible way to inhibit tumor growth by regulating aberrant metabolism. [ABSTRACT FROM AUTHOR]

Our study demonstrates that occupational exposure to nano-CaCO3 could lead to the poor pulmonary function observed among occupational workers. Oxidative stress participate in mechanisms of lung injury induced by nano-CaCO3. Especially, the results can provide information for proposing occupational strategies for reducing the occupational hazards. Objective: The aim of the study is to investigate whether nano–calcium carbonate (nano-CaCO3) occupational exposure could induce adverse health effects in workers. Methods: A cross-sectional study was conducted in a nano-CaCO3 manufacturing plant in China. Then, we have studied the dynamic distribution of nano-CaCO3 in nude mice and examined the oxidative damage biomarkers of subchronic administrated nano-CaCO3 on Sprague-Dawley rats. Results: The forced vital capacity (%) and the ratio of FEV1 to FVC is the rate of one second of workers were significantly decreased than unexposed individuals. Dynamic imaging in mice of fluorescence labeled nano-CaCO3 showed relatively high uptake and slow washout in lung. Similar to population data, the decline in serum glutathione level and elevation in serum MDA were observed in nano-CaCO3–infected Sprague-Dawley rats. Conclusions: We found that nano-CaCO3 exposure may result in the poor pulmonary function in workers and lead to the changes of oxidative stress indexes. [ABSTRACT FROM AUTHOR]

Epimedii Folium (EF) is a common traditional Chinese medicine that functions as a tonifying kidney yang to strengthen bones and muscles and dispel wind dampness (limb pain, lethargy, nausea, anorexia, and loose stools). Several studies have reported the potential risk of cholestatic liver damage from EF use; however, there have been few investigations of EF-induced cholestasis, particularly the underlying mechanisms. The purpose of this study was to evaluate the risk of EF-induced cholestasis in vivo and to explore the mechanisms of action. ICR mice were orally administered a water extract of EF (WEF) in doses of 6.5 and 19.5 g/kg/day for 14 weeks. Liver-to-body weight ratios, body weight, histopathological examination, and biochemical analyses were performed to assess WEF-induced cholestasis in the mice. Genes associated with bile acid (BA) metabolism and transport, including sodium taurocholate cotransporting polypeptide (NTCP), cytochrome P450 8B1 (CYP8B1), bile-salt export pump (BSEP), multidrug resistance P-glycoproteins 1 (MDR1), and farnesoid X receptor (FXR), were measured at the transcript and protein levels to investigate the potential mechanisms through which cholestasis is aroused by EF. After administration of WEF for 14 weeks, mice in the high-dose WEF group showed poor health with an increased liver-to-body weight ratio as well as higher serum aminotransferase, alkaline phosphatase, direct bilirubin, and total BA levels. Compared with the control group, mRNA expression of NTCP and cholesterol 7a-hydroxylase (CYP7A1) increased, and levels of BSEP, MDR1, multidrug resistance-associated protein 2, and multidrug resistance-associated protein 3 decreased in the WEF-treated group. NTCP, BSEP, MDR1, and CYP8B1 showed similar mRNA and protein expression trends. We demonstrated that the long-term oral administration of WEF causes cholestatic liver injury in mice, which is consistent with reported clinical cases. Furthermore, we found that the destruction of BA metabolism and transport is involved in WEF-induced cholestasis. The fine-scale molecular mechanisms of WEF-induced cholestasis and the active compounds of EF need further study. [Display omitted] • Prolonged ingestion induced cholestasis in mice. • It's consistent with clinical reports. • Bile acid disorder is involved. [ABSTRACT FROM AUTHOR]