Salvia miltiorrhiza suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.

In vivo antibacterial activity of medicinal plant Sophora flavescens against Streptococcus agalactiae infection.

Streptococcosis disease caused by Streptococcus agalactiae (Group B Streptococcus, GBS) results in a huge economic loss of tilapia culture. It is urgent to find new antimicrobial agents against streptococcosis. In this study, 20 medicinal plants were evaluated in vitro and in vivo to obtain medicinal plants and potential bioactive compounds against GBS infection. The results showed that the ethanol extracts of 20 medicinal plants had low or no antibacterial properties in vitro, with a minimal inhibitory concentration ≥256 mg/L. Interestingly, in vivo tests showed that 7 medicinal plants could significantly inhibit GBS infection in tilapia, and Sophora flavescens (SF) had the strongest anti-GBS activity in tilapia, reaching 92.68%. SF could significantly reduce the bacterial loads of GBS in different tissues (liver, spleen and brain) of tilapia after treated with different tested concentrations (12.5, 25.0, 50.0 and 100.0 mg/kg) for 24 h. Moreover, 50 mg/kg SF could significantly improve the survival rate of GBS-infected tilapia by inhibiting GBS replication. Furthermore, the expression of antioxidant gene cat, immune-related gene c-type lysozyme and anti-inflammatory cytokine il-10 in liver tissue of GBS-infected tilapia significantly increased after treated with SF for 24 h. Meanwhile, SF significantly reduced the expression of immune-related gene myd88 and pro-inflammatory cytokines il-8 and il-1ß in liver tissue of GBS-infected tilapia. The negative and positive models of UPLC-QE-MS, respectively, identified 27 and 57 components of SF. The major components of SF extract in the negative model were α, α-trehalose, DL-malic acid, D- (-)-fructose and xanthohumol, while in the positive model were oxymatrine, formononetin, (-)-maackiain and xanthohumol. Interestingly, oxymatrine and xanthohumol could significantly inhibit GBS infection in tilapia. Taken together, these results suggest that SF can inhibit GBS infection in tilapia, and it has potential for the development of anti-GBS agents.

Improving cleaner production of human activities to mitigate total petroleum hydrocarbons accumulation in coastal environment.

The marine coast is an important ecological transitional boundary but easily suffers from human intervention. Total petroleum hydrocarbons (TPHs) are ubiquitous along the coast. However, the influence of anthropogenic and natural factors on TPHs distribution remains unclear. This study sampled surficial sediment (N = 243) from the coasts of the largest peninsula-Leizhou Peninsula, in Southern China. We found that land-based discharge, sea traffic, and sediment type significantly (p < 0.05) drive the accumulation of TPHs. We observed that TPHs increased by 1.036 µg · g-1 (exp[αi] = exp. [0.0355]) of its original value with the addition of one more boat on the wharf. Although the average TPHs were at a moderate level (124.68, ND-1536.14, µg · g-1) and risk, 'Blue Carbon' ecosystems, i.e., mangroves (224.84, ND - 1441.13, µg · g-1, p < 0.001) were more severely polluted. Cleaner production policy should be applied to mitigate TPHs discharging trend from coastal areas.

Thermo-optically tunable slot waveguide-based dual mode-splitting resonators with enhanced sharp lineshapes.

Slot waveguide plays an essential role in achieving high-performance on-chip photonic sensors and nonlinear devices. Ideally, slot waveguide features a large evanescent field ratio and strong electric field intensity in the slot, leading to a high waveguide sensitivity. Unfortunately, the microring resonator (MRR) based on the slot waveguide suffers the less steep spectral slope due to the low quality factor induced by the huge optical propagation loss of the slot waveguide. In this work, a novel dual mode-splitting resonator based on the slot waveguide is proposed and demonstrated to steepen the slope of lineshapes. The device is implemented by two racetrack resonators based on a slot waveguide and a feedback waveguide to introduce coherent optical mode interference, which could induce mode-splitting resonance (MR) with sharp asymmetry line shape and large extinction ratio (ER). The proposed device is fabricated by the standard complementary metal-oxide-semiconductor (CMOS) technologies on silicon-on-insulator (SOI) platform, and the characterization results show dual MRs with an ER of 45.0 dB and a slope rate (SR) of 58.3 dB/nm, exhibiting a much steeper lineshape than that of the conventional MRR with slot waveguide. And the resonance can be tuned efficiently by applying various voltages of the TiN microheater. Investigations in dual MRs devices promote many potential applications in the field of optical switching, optical modulating, and on-chip optical sensing.

Selenium Status and Its Antioxidant Role in Metabolic Diseases.

Selenium (Se), in the form of selenoproteins, is an essential micronutrient that plays an important role in human health and disease. To date, there are at least 25 selenoproteins in humans involved in a wide variety of biological functions, including mammalian development, metabolic progress, inflammation response, chemoprotective properties, and most notably, oxidoreductase functions. In recent years, numerous studies have reported that low Se levels are associated with increased risk, poor outcome, and mortality of metabolic disorders, mainly related to the limited antioxidant defense resulting from Se deficiency. Moreover, the correlation between Se deficiency and Keshan disease has received considerable attention. Therefore, Se supplementation as a therapeutic strategy for preventing the occurrence, delaying the progression, and alleviating the outcomes of some diseases has been widely studied. However, supranutritional levels of serum Se may have adverse effects, including Se poisoning. This review evaluates the correlation between Se status and human health, with particular emphasis on the antioxidant benefits of Se in metabolic disorders, shedding light on clinical treatment.

[Effect of electroacupuncture on ocular surface sensory neuralgia and expression of P2X3 receptor and PKC in cornea and trigeminal ganglion of dry eye guinea pigs].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on ocular surface sensory neuralgia and the expression of P2X3 receptor (P2X3R) and protein kinase C(PKC)in cornea and trigeminal ganglion (TG) in dry eye disease (DED) guinea pigs, so as to explore its mechanism underlying improvement of ocular surface sensory neuralgia in DED. METHODS: Male British tricolor short haired guinea pigs were randomly divided into control, model, medication (pranoprofen), EA and sham acupuncture groups, with 8 guinea pigs in each group. The dry eye model was induced by subcutaneous injection of scopolamine hydrobromide solution (0.6 mg/0.2 mL,once daily) for 10 d. Guinea pigs in the medication group were treated by applying pranoprofen eye drops to eyes, 1 drop for one eye each time, three times a day. Guinea pigs of the EA group received EA stimulation (4 Hz/20 Hz,1 mA) of bilateral "Cuanzhu" (BL2) and "Taiyang" (HN5) and acupuncture at "Jingming" (BL1) "Sizhukong" (TE23), "Tongziliao" (GB1) for 15 min, once a day. Guinea pigs in the sham acupuncture group received blunt stimu-lation at the surface of the same acupoint with the tip of the acupuncture needle, once a day. All the treatments were conducted for 14 d. The corneal epithelium fluorescein staining score (0-3 points) was given according to the number of fluorescence-positive dots and flake-like coloration, the corneal mechanical perception thread (CMPT) detected using a corneal perception meter, and the palpebral fissure height measured. The number of sensory neurons in the cornea and TG was determined by using cholera toxin subunit B conjugated with Alexa Fluor 488 fluorescence labelling, and the expression levels of P2X3R and PKC in the cornea and TG detected by using immunohistochemistry and Western blot, separately. RESULTS: Compared with the control group, the corneal fluorescein staining score, immunoactivity and expression of P2X3R proteins in both cornea and TG, PKC proteins in TG were significantly increased (P<0.01), whereas the CMPT and the height of palpebral fissure and the number of TG neurons significantly decreased in the model group (P<0.05,P<0.01). In comparison with the model group, the fluorescein staining score in the medication and EA groups, the immunoactivity and expression of P2X3R in cornea and TG in the EA group, and that of TG PKC in the EA group and the sham acupuncture groups were significantly decreased (P<0.05, P<0.01), while the height of palpebral fissure and CMPT after EA and the number of labelling TG sensory neurons were remarkably increased in the EA group (P<0.01) rather than in the medication and sham acupuncture groups (P>0.05). CONCLUSION: EA can alleviate the damage of corneal epithelium and sensory neurons in dry eye model guinea pigs, which may be related to its functions in down-regu-lating the expression of P2X3R and PKC in the cornea and TG.

Tiankengomelania guangxiense, gen. et sp. nov., a dark septate endophytic fungus, promotes the growth of the medicinal orchid Dendrobium officinale.

Dendrobium officinale (Orchidaceae) is a traditional Chinese medicinal plant. Its growth is slow, however many dark septate endophytic fungi (DSEs) are considered useful to plant growth and as biocontrol agents against plant pathogens. The goals of this study were to identify a new DSE and evaluate its plant-growth promotion characteristics. Based on morphological and molecular phylogenetic evidence, a DSE fungal strain TK815 isolated from Dashiwei Tiankengs in Leye county Guangxi Province, China, was classified as a novel genus in the order Cheatothyriales, namely Tiankengomelania gen. nov. typified with T. guangxiense sp. nov. Tiankengomelania guangxiense TK815 can significantly promote the growth of D. officinale in stem length (11.25%), seedling height (16.97%), root length (10.34%), and dry weight (41.05%). This study discovered, described, and illustrated a new DSE fungus, and evaluated its biological function in contributing to the growth and production of the Chinese medicinal plant D. officinale.

Broadband Silicon Nitride Power Splitter Based on Bent Directional Couplers with Low Thermal Sensitivity.

Directional couplers, as power splitters, have provided a significant contribution for light splitting and combining in silicon photonics. However, the splitting ratio of conventional directional couplers is very sensitive to wavelength, which limits the bandwidth and the transmission performance of the devices. In this work, a silicon nitride bent directional coupler with large bandwidth, large fabrication tolerance, and low thermal sensitivity is proposed and demonstrated through simulation analysis and experiments. Moreover, the fabrication process of 400 nm thick silicon nitride photonic devices is described, which are compatible with complementary metal-oxide-semiconductor technology. The 1 dB bandwidth of the bent waveguide coupler can reach 80 nm, and the thermal sensitivity is reduced by 85% compared to the silicon-based devices.

Androgen is responsible for enhanced susceptibility of melatonin against traumatic brain injury in females.

BACKGROUND: Numerous publications have demonstrated that melatonin administration is associated with mortality reduction and improvement in neurological outcomes after traumatic brain injury (TBI). However, there are significant sex differences in several diseases associated with melatonin. We aimed to determine whether androgen was responsible for enhanced susceptibility of melatonin against TBI in females, as well as potential molecular mechanisms. METHODS: Weight-drop was used to establish a rodent model of TBI. Melatonin (10 mg/kg) and testosterone (1 mg/kg) were administered three times every day for three days after TBI using subcutaneous injection, respectively. Seven days after TBI, an open field assay was used to evaluate locomotor and exploratory activities. Neuronal amount, neuronal apoptosis, and expression of phosphorylated extracellularly regulated protein kinases 1/2 (ERK1/2), c-jun N-terminal kinase 1/2 (JNK1/2), and p38 mitogen-activated protein kinase (p38MAPK) in neurons were assessed using immunofluorescence assay seven days after TBI. The expression of caspase-3, Bax, and Bcl-2 in the frontal cortex was detected using western blot. RESULTS: Compared with female rats, melatonin administration exhibited more neuroprotective effects (including improved locomotor and exploratory activities, elevated neuronal amount, and reduced neuronal apoptosis) in male rats exposed to TBI. Moreover, testosterone significantly improved locomotor and exploratory activities, elevated neuronal amount, decreased neuronal apoptosis, downregulated phosphorylation of JNK1/2- and p38MAPK-positive neurons, but upregulated phosphorylation of ERK1/2-positive neurons in the frontal cortex, and reduced the expressions of cleaved caspase-3, Bax, but increased Bcl-2 expressions in female rats exposed to TBI. CONCLUSIONS: Androgen was responsible for the enhanced susceptibility to TBI under melatonin supplementation in females through a mechanism that may be associated with MAPK pathway regulation.

Synergistic anti-inflammatory effects of silibinin and thymol combination on LPS-induced RAW264.7 cells by inhibition of NF-κB and MAPK activation.

BACKGROUND: Combination drug therapy has become an effective strategy for inflammation control. The anti­inflammatory capacities of silibinin and thymol have each been investigated on its own, but little is known about the synergistic anti-inflammatory effects of these two compounds. PURPOSE: This study aims to investigate the synergistic anti-inflammatory effects of silibinin and thymol when administered in combination to lipopolysaccharide (LPS)-induced RAW264.7 cells. METHODS: RAW264.7 cells were pre-treated with silibinin and thymol individually or in combination for 2 h before LPS stimulation. Cell viability was detected by the MTT assay. Nitric oxide (NO) production was measured by Griess reagent. Reactive oxygen species (ROS) was evaluated by 2',7'-dichlorofluorescein-diacetate. ELISA was used to detect tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Western blot was performed to analyse the protein expression of LPS-induced RAW264.7 cells. RESULTS: We observed a synergistic anti-inflammatory effect of silibinin and thymol when administered in combination to LPS-induced RAW264.7 cells. Silibinin combined with thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) had more potent effects on the inhibition of NO, TNF-α, and IL-6 than those exerted by individual administration of these compounds in LPS-induced RAW264.7 cells. The combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) strongly inhibited ROS and cyclooxygenase-2 (COX-2). More importantly, the combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) was also successful in inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activities. Our results suggest that the synergistic anti-inflammatory effects of silibinin with thymol were associated with the inhibition of NF-κB and MAPK signalling pathways. CONCLUSION: The combination of silibinin and thymol (40 µM and 120 µM, respectively, with the molar ratio 1:3) could inhibit inflammation by suppressing NF-κB and MAPK signalling pathways in LPS-induced RAW264.7 cells.

Analysis of the clinical characteristics, drug treatments and prognoses of 136 patients with coronavirus disease 2019.

WHAT IS KNOWN AND OBJECTIVE: Since the December 2019 discovery of several cases of coronavirus disease 2019 (COVID-19) in Wuhan, China, the infection has spread worldwide. Our aim is to report on the clinical characteristics, treatments and prognoses of COVID-19. METHODS: This was a retrospective, single-centre, case series of 136 patients who were diagnosed with COVID-19 at Wuhan Third Hospital in Wuhan, China, between 28 January 2020 and 12 February 2020. The clinical characteristics, laboratory tests, treatment features and prognoses were summarized. RESULTS AND DISCUSSION: The 136 patients were divided into a moderate (M) group (n = 103, 75.7%) and a severe and critical (SC) group (n = 33, 24.3%). There were significant differences in the incidences of concomitant chronic medical illnesses (eg, hypertension, diabetes and cardiovascular disease), fever, dry cough and dyspnoea among the two groups (P < .05). Compared with those in the M group, lymphocyte count (LYM) decreased significantly in the SC group, while the serum levels of C-reactive protein (CRP), procalcitonin (PCT), creatinine (Cre), D-dimer, lactic dehydrogenase (LDH), myoglobin (MB) and troponin I (cTnl) increased significantly in the SC group (P < .05). The main therapeutic drugs were antivirals, antibiotics, glucocorticoids, immunomodulators, traditional Chinese medicine preparations and symptomatic support drugs. There were significant differences in the incidences of shock, myocardial injury, acute respiratory distress syndrome (ARDS) and renal injury among the two groups (P < .05). Among the 136 patients, 99 (72.7%) were cured, 14 (10.3%) were transferred to other hospital and 23 (16.9%) died. WHAT IS NEW AND CONCLUSION: Elderly patients with chronic diseases are more likely to develop severe or critical COVID-19 with multiple organ damage or systemic injuries. The improvement of LYM and CRP may be associated with the prognoses of COVID-19. The combined use of three or more antiviral drugs is to be avoided. The combination of broad-spectrum antibacterial drugs is not recommended and the risk of drug-induced liver injury should be monitored. Throughout a patient's hospitalization, their treatment plan should be evaluated and adjusted according to their vital signs, clinical symptoms, laboratory tests and imaging changes. Patients should receive effective psychological counselling.

Xuesaitong Protects Podocytes from Apoptosis in Diabetic Rats through Modulating PTEN-PDK1-Akt-mTOR Pathway.

Diabetic kidney disease (DKD) is a major cause of end-stage renal disease (ESRD), and therapeutic strategies for delaying its progression are limited. Loss of podocytes by apoptosis characterizes the early stages of DKD. To identify novel therapeutic options, we investigated the effects of Xuesaitong (XST), consisting of total saponins from Panax notoginseng, on podocyte apoptosis in streptozotocin- (STZ-) induced diabetic rats. XST (5 mg/kg·d) or Losartan (10 mg/kg·d) was given to diabetic rats for 12 weeks. Albuminuria, renal function markers, and renal histopathology morphological changes were examined. Podocyte apoptosis was determined by triple immunofluorescence labelling including a TUNEL assay, WT1, and DAPI. Renal expression of Nox4, miRNA-214, PTEN, PDK1, phosphorylated Akt, mTOR, and mTORC1 was detected. In diabetic rats, severe hyperglycaemia and albuminuria developed, and apoptotic podocytes were markedly increased in diabetic kidneys. However, XST attenuated albuminuria, mesangial expansion, podocyte apoptosis, and morphological changes of podocytes in diabetic rats. Decreased expression of PTEN, as well as increased expression of Nox4, miRNA-214, PDK1, phosphorylated Akt, mTOR, and mTORC1, was detected. These abnormalities were partially restored by XST treatment. Thus, XST ameliorated podocyte apoptosis partly through modulating the PTEN-PDK1-Akt-mTOR pathway. These novel findings might point the way to a natural therapeutic strategy for treating DKD.

Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/ß-Catenin Signaling Pathway in STZ-Induced Diabetic Rats.

INTRODUCTION: Epithelial-mesenchymal transition (EMT) may contribute to podocyte dysfunction in diabetic nephropathy (DN). Aiming to identify novel therapeutic options, we investigated the protective effects of Panax notoginseng (PN) on podocyte EMT in diabetic rats and explored its mechanisms. METHODS: Diabetes was induced in rats with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg. Diabetic rats were randomly divided into three groups, namely, diabetic rats, diabetic rats treated with beraprost sodium (BPS) at 0.6 mg/kg/d or PN at 0.4 g/kg/d p.o., for 12 weeks. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology, and podocyte morphological changes were evaluated. Protein expression of EMT markers (desmin, α-SMA, and nephrin) as well as components of the Wnt/ß-catenin pathway (wnt1, ß-catenin, and snail) was detected by immunohistochemistry and Western blot, respectively. RESULTS: In diabetic rats, severe hyperglycemia and albuminuria were detected. Moreover, mesangial expansion and podocyte foot process effacement were found markedly increased in diabetic kidneys. Increased protein expression of wnt1, ß-catenin, snail, desmin, and α-SMA, as well as decreased protein expression of nephrin was detected in diabetic kidneys. All these abnormalities found in DN rats were partially restored by PN treatment. CONCLUSION: PN ameliorated albuminuria and podocyte EMT in diabetic rats partly through inhibiting Wnt/ß-catenin signaling pathway. These findings provide experimental arguments for a novel therapeutic option in DN.

Astragalus membranaceus and Panax notoginseng, the Novel Renoprotective Compound, Synergistically Protect against Podocyte Injury in Streptozotocin-Induced Diabetic Rats.

This study was aimed at investigating the synergistical protective effects of Astragalus membranaceus (AG) and Panax notoginseng (NG) on podocyte injury in diabetic rats. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at 55 mg/kg. Diabetic rats were then orally administrated with losartan, AG, NG, and AG plus NG (2 : 1) for 12 weeks. Albuminuria, biochemical markers, renal histopathology, and podocyte number per glomerulus were measured. Podocyte apoptosis was determined by triple immunofluorescence labeling including TUNEL assay, WT1, and DAPI. Renal expression of nephrin, α-dystroglycan, Bax, Bcl-xl, and Nox4 was evaluated by immunohistochemistry, western blot, and RT-PCR. AG plus NG ameliorated albuminuria, renal histopathology, and podocyte foot process effacement to a greater degree than did AG or NG alone. The number of podocytes per glomerulus, as well as renal expression of nephrin, α-dystroglycan, and Bcl-xl, was decreased, while podocyte apoptosis, as well as renal expression of Bax and Nox4, was increased in diabetic rats. All of these abnormalities were partially restored by AG plus NG to a greater degree than did AG or NG alone. In conclusion, AG and NG synergistically ameliorated diabetic podocyte injury partly through upregulation of nephrin, α-dystroglycan, and Bcl-xl, as well as downregulation of Bax and Nox4. These findings might provide a novel treatment combination for DN.

Effects and mechanism of action of Huang-Lian-Jie-Du-Tang in atopic dermatitis-like skin dysfunction in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD), a disorder prevalent during childhood and adulthood, seriously affects the patient's quality of life. Although Huang-Lian-Jie-Du-Tang (HLJDT) has shown anti-inflammatory effects in previous studies, its effects and mechanism of action underlying AD disorder are still largely unknown. OBJECTIVE: This study explored the anti-inflammatory and immunomodulatory effects of HLJDT on the AD-like dermal disorder, induced in vitro by lipopolysaccharide (LPS)-triggered inflammation, and in vivo by 2,4-dinitrochlorobenzene (DNCB). MATERIALS AND METHODS: In vivo HLJDT effects were investigated by determining the severity of dermatitis, which consisted of observing signs of skin lesions, visually and through haematoxylin and eosin (HE) staining, in mouse ears and dorsal skin, measuring serum levels of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, interferon (IFN)-γ, the tumour necrosis factor (TNF)-α, and determining the splenic index, number of splenic CD4+/CD8+ T-lymphocytes, as well as the phosphorylation levels of mitogen-activated protein kinases (including MAPKs-p38, ERK, and JNK), IκB-α, and nuclear factor kappa B (NF-κB) (p65) within dermal lesions. Morphological changes in LPS-induced inflammation were observed under a microscope, and ELISA and qPCR assays were used to measure IL-1α, IL-1ß, IL-6, and TNF-α expression levels. The protein expression levels of P-ERK/ERK, P-p38/p38, P-JNK/JNK, P-IKß-α, and P-p65 were measured through western blotting. Additionally, p65 expression was assessed by immunofluorescence, and LPS binding to RAW264.7 cell membrane was studied with laser confocal microscopy. RESULTS: HLJDT could remarkably mitigate DNCB-induced AD-like lesion symptoms, alleviating inflammatory mediator infiltration in mouse ears and dorsal skin tissue, down-regulating serum expression levels of IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IFN-γ, and TNF-α, normalising the splenic CD4+/CD8+ T-lymphocyte ratio, and inactivating MAPKs (including p38, ERK, and JNK), IκB-α, and NF-κB (p65) in dorsal skin. Furthermore, HLJDT inhibited LPS-induced differentiation of RAW264.7 cells, as evidenced by the decreased protein and mRNA expression of IL-1α, IL-1ß, IL-6, and TNF-α. Additionally, it decreased ERK, p38, JNK, IKß-α, and p65 phosphorylation levels in the MAPKs/NF-κB pathway, inhibited p65 nuclear translocation, and reduced LPS binding to the RAW264.7 cell membrane. CONCLUSIONS: HLJDT significantly improved AD-like symptoms via inhibition of the MAPKs/NF-κB pathway. Therefore, administration of HLJDT might be a potential treatment for AD in the clinical setting.

Rheum palmatum extract exerts anti-hepatocellular carcinoma effects by inhibiting signal transducer and activator of transcription 3 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) is among the most common malignancies. Signal transducer and activator of transcription 3 (STAT3), with abnormal expression and constitutive activation, has been reported to promote proliferation, metastasis, survival and angiogenesis of HCC cells. Rheum palmatum (RP), a traditional Chinese medicinal herb, exhibited tumor-suppressing effects in multiple human cancers, but its potential functions in HCC remain unexplored. AIM OF THE STUDY: This study aimed to examine the involvement of STAT3 signaling in the anti-HCC effects of RP extract. MATERIALS AND METHODS: SMMC-7721 and HepG2 HCC cell lines were treated with RP extract for 24 h, and then viability, migration, and invasion of HCC cells and angiogenesis of human umbilical vein endothelial cells (HUVECs) were analyzed using MTS, wound-healing, Transwell invasion and tube formation assays, respectively. Western blotting and immunohistochemistry (IHC) were used to examine the activation of key molecules in STAT3 signaling, including STAT3, JAK2, and Src. Additionally, we explored the in vivo antitumor effects of RP extract in a xenograft tumor nude mouse model of HCC. RESULTS: The result showed that RP extract reduced viability, migration, and invasion of SMMC-7721 and HepG2 cells and angiogenesis of HUVECs. It suppressed the phosphorylation of STAT3 and its upstream kinases including JAK2 and Src. In addition, RP extract treatment downregulated STAT3 target genes, including survivin, Bcl-xL, Mcl-1, Bcl-2, MMP-2, MMP-9, Cyclin D1, CDK4, c-Myc, and VEGF-C. Furthermore, RP extract suppressed the xenograft tumor growth and activation of STAT3 in xenograft tumor mice. CONCLUSION: Collectively, the results showed that RP extract prevented HCC progression by inhibiting STAT3, and might be useful for the treatment of HCC.

Anti-inflammatory and immune response regulation of Si-Ni-San in 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS) is a well-known decoction in traditional Chinese medicine. Although studies have indicated that the anti-inflammatory and anti-allergic properties of SNS and its components can account for their therapeutic effects, the role and mechanism of SNS in treating skin dysfunction remain unclear. AIM OF THE STUDY: Atopic dermatitis (AD), a disorder known for its prevalence in infants and adults, severely influences the quality of life of affected patients. In this study, we aimed to investigate the anti-inflammatory and immune response modulations of SNS in 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin dysfunction. MATERIALS AND METHODS: Dermatitis was induced in Kunming mice by the topical application of DNCB. SNS or dexamethasone (positive control) was topically applied every day over the course of the 21-day study. The following were assessed: dermatitis severity scores; ear and dorsal skin haematoxylin and eosin staining; interleukin (IL)- 1α, IL-1ß, IL-2, IL-4, IL-6, and tumour necrosis factor (TNF)-α cytokine levels in the serum; spleen index; spleen CD4 + /CD8 + T lymphocyte ratio; and phosphorylation levels of mitogen-activated protein kinases (MAPKs- p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK)), IκB-α, and nuclear factor (NF)-κB (p65) in skin lesions. RESULTS: SNS significantly alleviated the symptoms of AD-like lesions induced by DNCB, decreased the infiltration of inflammatory cells in the ear and dorsal tissues, suppressed the increased cytokine levels in the serum, reduced the CD4 + /CD8 +T lymphocyte ratio in the spleen, and downregulated the activation of MAPKs, IκB-α, and NF-κB (p65) in the dorsal skin. The effects were similar to those of dexamethasone. CONCLUSIONS: SNS alleviated the DNCB-induced AD-like skin dysfunction in mice through anti-inflammatory and immune system modulation, indicating that SNS shows potential for AD treatment in clinical settings.

The effects of freeze-dried Ganoderma lucidum mycelia on a recurrent oral ulceration rat model.

BACKGROUND: Conventional scientific studies had supported the use of polysaccharides and ß-glucans from a number of fungi, including Ganoderma lucidum for the treatment of recurrent oral ulceration (ROU). Our aim of the present study was to evaluate whether freeze-dried powder from G. lucidum mycelia (FDPGLM) prevents ROU in rats. METHODS: A Sprague-Dawley (SD) rat model with ROU was established by autoantigen injection. The ROU rats were treated with three different dosages of FDPGLM and prednisone acetate (PA), and their effects were evaluated according to the clinical therapeutic evaluation indices of ROU. RESULTS: High-dose FDPGLM induced significantly prolonged total intervals and a reduction in the number of ulcers and ulcer areas, thereby indicating that the treatment was effective in preventing ROU. Enzyme-linked immunosorbent assay (ELISA) showed that high-dose FDPGLM significantly enhanced the serum transforming growth factor-ß1 (TGF-ß1) levels, whereas reduced those of interleukin-6 (IL-6) and interleukin-17 (IL-17). Flow cytometry (FCM) showed that the proportion of CD4+ CD25+ Foxp3+ (forkhead box P3) regulatory T cells (Tregs) significantly increased by 1.5-fold in the high-dose FDPGLM group compared to that in the rat model group (P < 0.01). The application of middle- and high-dose FDPGLM also resulted in the upregulation of Foxp3 and downregulation of retinoid-related orphan receptor gamma t(RORγt) mRNA. CONCLUSION: High-dose FDPGLM possibly plays a role in ROU by promoting CD4+ CD25+ Foxp3+ Treg and inhibiting T helper cell 17 differentiation. This study also shows that FDPGLM may be potentially used as a complementary and alternative medicine treatment scheme for ROU.

[Research progress of iron metabolism in critical ill patients].

OBJECTIVE: Iron is an essential nutrient element for human, but has potential toxicity. Under physiological conditions, the processes of iron absorption, transportation, cellular uptake and utilization, storage, release, excretion as well as regulation of iron metabolism maintain the iron homeostasis. However under pathological conditions, the iron metabolism changes and is associated with the pathological states. In order to realize the relationship between the critical illness status and the iron metabolism, we start with an analysis of the basic processes of iron metabolism in human and the toxicity of iron, followed by summary on the alteration of iron metabolism in the settings of pathological conditions, such as inflammation, infection and anemia, which often occur in critical illness. Then, we discuss the relationship between the prognosis and the parameters of iron metabolism. Moreover, we review the current researches on treatments related to iron metabolism, which involve the iron supplementation, iron chelation and agents regulating iron metabolism.

QuantFusion: Novel Unified Methodology for Enhanced Coverage and Precision in Quantifying Global Proteomic Changes in Whole Tissues.

Single quantitative platforms such as label-based or label-free quantitation (LFQ) present compromises in accuracy, precision, protein sequence coverage, and speed of quantifiable proteomic measurements. To maximize the quantitative precision and the number of quantifiable proteins or the quantifiable coverage of tissue proteomes, we have developed a unified approach, termed QuantFusion, that combines the quantitative ratios of all peptides measured by both LFQ and label-based methodologies. Here, we demonstrate the use of QuantFusion in determining the proteins differentially expressed in a pair of patient-derived tumor xenografts (PDXs) representing two major breast cancer (BC) subtypes, basal and luminal. Label-based in-spectra quantitative peptides derived from amino acid-coded tagging (AACT, also known as SILAC) of a non-malignant mammary cell line were uniformly added to each xenograft with a constant predefined ratio, from which Ratio-of-Ratio estimates were obtained for the label-free peptides paired with AACT peptides in each PDX tumor. A mixed model statistical analysis was used to determine global differential protein expression by combining complementary quantifiable peptide ratios measured by LFQ and Ratio-of-Ratios, respectively. With minimum number of replicates required for obtaining the statistically significant ratios, QuantFusion uses the distinct mechanisms to "rescue" the missing data inherent to both LFQ and label-based quantitation. Combined quantifiable peptide data from both quantitative schemes increased the overall number of peptide level measurements and protein level estimates. In our analysis of the PDX tumor proteomes, QuantFusion increased the number of distinct peptide ratios by 65%, representing differentially expressed proteins between the BC subtypes. This quantifiable coverage improvement, in turn, not only increased the number of measurable protein fold-changes by 8% but also increased the average precision of quantitative estimates by 181% so that some BC subtypically expressed proteins were rescued by QuantFusion. Thus, incorporating data from multiple quantitative approaches while accounting for measurement variability at both the peptide and global protein levels make QuantFusion unique for obtaining increased coverage and quantitative precision for tissue proteomes.