Advancements in ferroptosis research and therapeutic strategies for alcoholic liver disease: a narrative review.

Ferroptosis is a novel mechanism of programmed cell death characterized by an iron overload-induced lipid peroxidation cascade. The incidence of alcoholic liver disease (ALD) is rising globally, contributing to markedly high morbidity and mortality. ALD pathogenesis is an intricate and continuously evolving process. Several basic and clinical investigations have established a correlation between ferroptosis and ALD initiation and progression. Additionally, anti-ferroptosis drugs have demonstrated effectiveness in ameliorating alcohol-induced liver injury. This review aims to provide an overview of recent advancements in ferroptosis research pertaining to ALD, encompassing imbalance of antioxidant systems, iron overload, autophagy, mitochondria, epigenetic changes, and prospective therapeutic drugs targeting ferroptosis. Our aim is to reveal the potential of ferroptosis-related diagnoses and therapeutic interventions for the treatment of ALD.

On the mechanism of dendritic fragmentation by ultrasound induced cavitation.

A dedicated solidification device and high speed camera were used to capture dendritic fragmentation of pure succinonitrile (SCN) induced by oscillating ultrasonic bubbles. Theoretical analysis of the melting behavior of the dendrite was performed based on local solidification thermodynamics. The dendritic growth or the evolution of the solid-liquid interface is closely related to both thermodynamics of the cavitation bubble and the local geometry of the dendrite. Accordingly, for the first time, a dimensionless scaling formulation was developed by fitting both theoretical and experimental data to determine the variational pressure exerted by the cavitation bubble.

Bilateral Clavicular Fracture with Unilateral Scapular Fracture.

The aim of this report is to present a rare case of bilateral clavicular fracture with a unilateral scapular fracture of a young patient following high-velocity trauma without any comorbidity. Clavicle fracture is common however, simultaneously, both clavicle and scapular fracture is a rare entity. The incidence of bilateral clavicle fracture is 0.43% of clavicle fractures with an overall incidence of between 0.011 and 0.017%. According to our knowledge, no similar case has been reported. We present a case of 35 years old male who encountered a high energy trauma with a resulting right-sided comminuted midshaft clavicle fracture with the ipsilateral displaced scapular body fracture and left-sided midshaft clavicular fracture. He underwent open reduction and internal fixation. The range of movements of both acrominoclavicular joints was satisfactory after three months of follow-up. Open reduction and internal fixation resulted in a good outcome.

[High-Content siRNA Screen of the Kinome Identifies Kinases Involved in Git2-Induced Mesenchymal-Epithelial Transition].

Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) programs are involced in the metastatic process. More and more evidence confirms that EMT is vital for the initiation and dissemination of cancer cells whereas MET is critical for successful metastatic colonization of a secondary organ. The regulating mechanism of EMT mediated cancer progression and metastasis has been deeply investigated. However, what processes are dependent on MET in metastatic cascades remains unclear. Here, we created a cell based high-content siRNA screen using the breast cancer cell line 4TO7 to search for kinases that were involved in Git2-induced MET. Our results revealed that 58 kinases including transferase, phosphorylation regulators, ATP/nucleotide partners potentially participate in Git2-induced MET. Our preliminary data is expected to facilitate elucidation of the mechanism on how MET is initiated during cancer metastasis.

Systemic ALA-PDT effectively blocks the development of psoriasis-like lesions and alleviates leucocyte infiltration in the K14-VEGF transgenic mouse.

BACKGROUND: Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders. In spite of significant advances in the treatment of psoriasis, more effective and safer therapeutic strategies are still needed. Photodynamic therapy (PDT) is a method of light treatment that is being used increasingly in the treatment of dermatological diseases. AIM: To evaluate the therapeutic effects of systemic 5-aminolaevulinic acid (ALA)-PDT on psoriasis and to explore its potential mechanism of action. METHODS: We investigated the therapeutic effects of systemic ALA-PDT in K14-vascular endothelial growth factor (VEGF) transgenic homozygous mice, an animal model of psoriasis, which has many clinical and histopathological characteristics similar to those of human psoriasis. Using haematoxylin and eosin staining, immunohistochemistry and real-time quantitative PCR respectively, we assessed the changes in psoriasis-like lesions, cellular infiltration of T cells, dendritic cells (DCs) and neutrophils, and the mRNA expression of the inflammatory cytokines interleukin (IL)-17 and interferon (IFN)-γ in the lesions. RESULTS: Systemic ALA-PDT blocked the development of psoriasis-like lesions and moderately attenuated the histopathological changes in K14-VEGF transgenic mice. Furthermore, systemic ALA-PDT produced an obvious reduction in infiltration of T cells, CD11c+ DCs and neutrophils in psoriasis-like lesions. In addition, systemic ALA-PDT also significantly decreased the mRNA expression of IL-17 and IFN-γ. CONCLUSIONS: We suggest that the mechanism of systemic ALA-PDT in this psoriasis-like model might be associated with selective damage to abnormal T helper (Th)1 and Th17 cells, and reduction of the inflammatory cytokines IL-17 and IFN-γ. These observations partly explain the potential mechanism of systemic ALA-PDT in psoriasis and other inflammatory skin diseases.

Anti-TWEAK monoclonal antibodies reduce vascular damage and leucocyte infiltration in a mouse model of cutaneous reverse passive Arthus reaction.

BACKGROUND: Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a pro-inflammatory cytokine, which is closely associated with the pathogenesis of various types of cutaneous vasculitis (CV). AIM: To investigate the therapeutic effects of an anti-TWEAK monoclonal antibody (mAb) in a mouse model of cutaneous reverse passive Arthus (RPA) reaction. METHODS: Cutaneous RPA reaction was induced in BALB/c mice by intradermal injection of anti-ovalbumin IgG into the left ear followed immediately by intravenous injection of chicken ovalbumin. After treatment, haemorrhagic lesions in the mouse skin were scored semiquantitatively. The amount of extravasated fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) in the ears was detected spectrophotometrically. Expression of myeloperoxidase (MPO) was detected by immunohistochemical staining, while mRNA expression of TNF-α and interleukin (IL)-6 in lesional skin was detected by real-time quantitative (q)PCR. RESULTS: Our results indicated that anti-TWEAK mAb significantly attenuated the clinical and histopathological changes in immune complex (IC)-induced mice, and also reduced the semiquantitative haemorrhage score, FITC-labelled BSA extravasation and MPO activity. Real-time qPCR showed that anti-TWEAK mAb significantly inhibited mRNA expression of TNF-α and IL-6 in lesional skin from IC-induced mice. CONCLUSION: These data suggest that anti-TWEAK mAb can block vascular damage and leucocyte infiltration in IC-induced mice. TWEAK might be a candidate immunotherapeutic medicine for suppression of IC-induced CV.

[Effects of prenatal maternal seizure on hippocampal damage and cognitive deficits in offspring rats].

Objective: To observe hippocampal damage and cognitive impairment of offspring exposed to prenatal maternal seizure induced by amygdala kindling, and to explore the underlying mechanism by the detection of pathological changes of placenta. Method: Adult female SD rats were randomly divided into three groups: control group(8 rats), kindling group(12 rats) and sham group(8 rats). All the rats were allowed to mate after one week's fully kindling. The pregnant rats in kindling group received electric stimulation every 48 h. Dams were allowed to deliver naturally. Effects of maternal seizure on the number of offspring, the survival rate and body weight of pups were observed. HE staining was used to visualize histopathological changes of placenta. Morris water maze test was used to assess the cognitive function and Nissal's staining to detect hippocampal morphology of the offspring. One-way ANOVA analysis and χ2 test were used. Result: Compared with the sham group (95%(78/82)) and the control group (95%(82/86)), the survival rate of pups in kindling group(81%(66/82))was much lower (χ2=13.817, P=0.001). There were no significant differences in the number of pups per litter and pups birth-weight between kindling group and sham group or control group(F=0.312 and 0.257, P=0.736 and 0.776). HE staining showed that placental tissues from control and sham groups were normal whereas the histologic abnormalities of placentas from kindling group were characterized by thickening of the villus vascular walls, luminal stenosis, trophoblasts hyperplasia, abnormalities of trophoblasts with nuclear pyknosis and karyorrhexis and accumulation of inflammatory lymphocytes in labyrinthine zone. Nissl staining showed that neurons in hippocampus of P0(0 d after birth) and P84(84 d after birth) offspring from control and sham groups were normal, but neuronal damages were obvious in hippocampus of P0 and P84 offspring from kindling groups, and the damages in P0 pups were severe with a marked loss of neuron, shrinkage of cells and nuclear pyknosis and karyorrhexis. In the Morris water maze, compared with the sham group ((29±8), (19±9), (10±4)s) and the control group ((25±6), (17±5), (14±4)s) rats in the kindling group ((36±8), (29±8), (30±11)s) exhibited significantly longer escape latency from the 3rd, 4th, and 5th days (F=6.276, 7.518, 18.422, P=0.030, 0.003, 0.000), significant less time in the target quadrant ((27±8) vs.(58±11)and(68±13)s, F=35.993, P=0.000) and reduced number of crossing the platform ((4.4±1.7) vs. (7.2±1.6) and (8.5±1.3)times, F=18.377, P=0.000). In addition, there was no significant difference between control and sham groups(P all >0.05). Conclusion: The prenatal maternal seizures induced significant pathological damages to hippocampus and cognitive impairment of offspring. Hypoxia-ischemia of placenta might play an important role in this process.

[Effect of GTPase activating protein Git2 on metastasis in breast cancer].

OBJECTIVE: To investigate the effect of GTPase activating protein Git2 on metastasis in breast cancer. METHODS: Git2 gene over-expression was induced by Git2 cDNA, and Git2 gene knockdown was induced by Git2 ShRNA lentivirus in four breast cancer cell lines. Six-week old wide type female mice were also used in this study. The cells were tagged with luciferase and injected into wide type female mice by tail vein or 4(th) mammary fat pad, respectively, to establish a cancer metastasis model. In vivo real time imaging system and immunohistochemical staining were used to detect the cancer metastasis. RESULTS: The relative mRNA expression level of Git2 (normalized by GAPDH) in the 4T1, 4TO7, 168FARN and 67NR cells were 0.91±0.03, 0.125±0.06, 0.131±0.04 and 0.92±0.04, respectively. The expression of EMT marker E-cadherin was inhibited and N-cadherin and vimentin were enhanced when Git2 was over-expressed in 168FARN cells and 4TO7 cells expressing low level of Git2, whereas the expression of E-cadherin was increased and N-cadherin and vimentin were decreased when Git2 was knocked down in 67NR cells and 4T1 cells expressing high level of Git2. Furthermore, over-expression of Git2 promoted 4TO7 cells to progress from micro-metastasis to macro-metastasis. The down-regulation of Git2 pushed 67NR cells to intravasate into blood circulation and suppressed the metastatic ability of 4T1 cells. The number of bioluminescence photos of lung metastatic 4T1-Luc-KD cells was (0.4±0.05)×10(6,) compared with (3.0±0.04)×10(6) in the control 4T1-Luc cells, showing a significant difference (P<0.05). CONCLUSION: Our results indicate that Git2 is involved in breast cancer initiation and metastatic colonization.

Comprehensive analysis of phenotypes and genetics in 21 Chinese families with haemophilia B: characterization of five novel mutations.

Molecular characterization of haemophilia B (HB) at the factor IX gene (F9) is essential to establish diagnosis, confirm genotype-phenotype correlations and to advise in genetic counselling. This study aimed to identify the causative mutations in 21 Chinese families with HB and to analyse the association of these mutations with clinical phenotype. Phenotypic analyses were performed using one-stage assay for factor IX (FIX) activity (FIX: C) and enzyme-linked immunosorbent assay for FIX antigen (FIX: Ag). Direct sequencing of the F9 gene was carried out. For those suspected to have a large deletion, multiplex ligation-dependent probe amplification (MLPA) was performed. Predicting the causal impact of new changes was studied by bioinformatics approaches. We also assessed the effect of the F9 mutations on the FIX protein structure and function. Causative mutations were detected in all study patients. There were 14 point mutations, three small deletions, one large deletion and one small in-frame duplication that together comprised a total of 19 unique variants, of which five were novel. The structural and functional defects of novel missense and in-frame deletion/duplication mutations were demonstrated by bioinformatics approaches. The 12 missense mutations include five purely quantitative mutations, five predominantly qualitative abnormalities and two combined defects. Our data confirmed the genetic heterogeneity of the F9 mutations. Quantitative missense mutations were found to be in different regions of precursor FIX compared with qualitative and combined ones.

Construction of the industrial ethanol-producing strain of Saccharomyces cerevisiae able to ferment cellobiose and melibiose.

The gene mel1, encoding alpha-galactosidase in Schizosaccharomyces pombe, and the gene bgl2, encoding and beta-glucosidase in Trichoderma reesei, were isolated and co-expressed in the industrial ethanol-producing strain of Saccharomyces cerevisiae. The resulting strains were able to grow on cellobiose and melibiose through simultaneous production of sufficient extracellular alpha-galactosidase and beta-glucosidase activity. Under aerobic conditions, the growth rate of the recombinant strain GC 1 co-expressing 2 genes could achieve 0.29 OD600 h(-1) and a biomass yield up to 7.8 g l(-1) dry cell weight on medium containing 10.0 g l(-1) cellobiose and 10.0 g l(-1) melibiose as sole carbohydrate source. Meanwhile, the new strain of S. cerevisiae CG 1 demonstrated the ability to directly produce ethanol from microcrystalline cellulose during simultaneous saccharification and fermentation process. Approximately 36.5 g l(-1) ethanol was produced from 100 g of cellulose supplied with 5 g l(-1) melibose within 60 h. The yield (g of ethanol produced/g of carbohydrate consumed) was 0.44 g/g, which corresponds to 88.0% of the theoretical yield.

Tumour necrosis factor-like weak inducer of apoptosis (TWEAK), an important mediator of endothelial inflammation, is associated with the pathogenesis of Henoch-Schonlein purpura.

Tumour necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumour necrosis factor (TNF) family, has been implicated as a proinflammatory cytokine in many types of autoimmune and infectious diseases. However, information about TWEAK in dermatological diseases is limited. Herein, we investigated the role of TWEAK in patients with Henoch-Schonlein purpura (HSP) and the ability of TWEAK on chemokine production in the human dermal microvascular endothelial cell line (HMEC-1). Serum TWEAK levels in patients with HSP, together with patients with psoriasis vulgaris (PV) and atopic dermatitis (AD), were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with TWEAK at concentrations ranging from 1 ng/ml to 100 ng/ml. Serum levels of TWEAK were elevated in patients with HSP in the acute stage but not in patients with PV or AD. Moreover, TWEAK levels were correlated with the severity of HSP. TWEAK markedly induced CCL5 and CXCL8 production at both mRNA and protein levels in HMEC-1 cells. In addition, TWEAK-stimulated HMEC-1 supernatant enhanced HL-60 or human acute monocytic leukaemia cell line (THP-1) cell migration. Finally, Western blot data revealed that TWEAK can induce rapid phosphorylation of inhibitor of κB-α (IκBα) in HMEC-1 cells. In conclusion, we show that serum levels of TWEAK were elevated in patients with acute stage HSP. TWEAK may act as a regulator of nuclear factor-κB (NF-κB) activation and chemokine production in human dermal microvascular endothelial cells, thus promoting leucocyte migration in cutaneous vasculitis.

Electrochemical hydrogen storage in single-walled carbon nanotube paper.

Single-walled carbon nanotube (SWNT) papers were successfully prepared by dispersing SWNTs in Triton X-100 solution, then filtered by PVDF membrane (0.22 microm pore size). The electrochemical behavior and the reversible hydrogen storage capacity of single-walled carbon nanotube (SWNT) papers have been investigated in alkaline electrolytic solutions (6 N KOH) by cyclic voltammetry, linear micropolarization, and constant current charge/discharge measurements. The effect of thickness and the addition of carbon black on hydrogen adsorption/desorption were also investigated. It was found that the electrochemical charge-discharge mechanism occurring in SWNT paper electrodes is somewhere between that of carbon nanotubes (physical process) and that of metal hydride electrodes (chemical process), and consists of a charge-transfer reaction (Reduction/Oxidation) and a diffusion step (Diffusion).

Effect of Ga and Mn doping on structural, electrical transport and magnetic properties of Na(0.75)CoO(2).

The effects of doping with magnetic Mn ions or nonmagnetic Ga ions on the structural, electrical transport and magnetic properties of Na(0.75)CoO(2) have been investigated. It has been found that the lattice parameter c of the samples increases with Ga or Mn ion doping. Ga doping raises the electrical resistivity of Na(0.75)CoO(2), but the metallic conducting behaviour of the compound has not been influenced. In contrast, 5% Mn doping leads to a metal-insulator transition at low temperatures in Na(0.75)Co(1-y)Mn(y)O(2). The susceptibility of the Ga doped sample shows strong magnetic field dependence, while the susceptibility of the Mn doped samples is not very sensitive to the magnetic field. This work implies that magnetic interaction plays an important role in Na(x)CoO(2).

Characterization of nanoparticles of LiMn2O4 synthesized by a one-step intermediate-temperature solid-state reaction.

Nanoparticles of lithium manganese oxide (LiMn2O4) with a spinel structure have been synthesized by a one-step intermediate temperature solid-state reaction. The influence of the molar ratio of citric acid to the metal ions on the physicochemical properties of LiMn2O4 powders in air has been analyzed by means of X-ray diffraction and electron microscope techniques. The electrochemical behavior of the material has been examined by charge/discharge tests and cyclic voltammetry. Test results reveal that LiMn2O4 particles with lower molar ratios of citric acid to metal ions (1:2) are highly crystalline and highly electrochemically reversible, with better cycle capabilities when compared with a sample with a higher molar ratio (2:1). The LiMn2O4 powders obtained by this method have a uniform morphology with a narrow size distribution.

Topical application of penciclovir cream for the treatment of herpes simplex facialis/labialis: a randomized, double-blind, multicentre, aciclovir-controlled trial.

BACKGROUND: Herpes simplex facialis/labialis (HSFL) is a common infectious skin disorder, caused mainly by herpes simplex virus (HSV) type 1, for which the topical application of a cream containing an antiviral agent for treatment of the disease has been widely utilized. OBJECTIVE: To explore the efficacy of the topical application of 1% penciclovir cream in the treatment of HSFL, and to compare its efficacy and safety with 3% aciclovir cream. METHODS: A total of 248 patients with a diagnosis of HSFL were randomly allocated to one of the two treatment groups (n = 124 each), using stratified randomization based on a table of random numbers. Before treatment (day 0) and at every visit (days 3, 5 and 7) during the study, the sign and symptom scores were recorded by the same doctor. RESULTS: Excluding 23 patients (10 in the penciclovir and 13 in the aciclovir groups), 225 completed the study, and no severe adverse events were noted with any of the treatment regimens. Results show that an encouraging improvement in the clinical course was found simultaneously for patients with each episode type and each treatment assignment. There were no significant differences in terms of efficacy endpoint, clinical cure rate, and safety between the two treatment arms, but there was a trend towards a shorter time to resolution of all symptoms, cessation of new blisters, and loss of crust (p

Nanocrystalline alpha-Ni(OH)2 prepared by ultrasonic precipitation.

Nanocrystalline alpha-Ni(OH)2 was prepared by an ultrasonic precipitation/stirring method. Results of X-ray diffraction, transmission electron microscopy, infrared, and thermogravimetric measurements confirm that the sample obtained is alpha phase. Compared with the sample prepared without ultrasonic stirring, the crystal structure of the alpha phase sample has been changed from beta phase. The crystalline size of the sample is about 20 nm, which is smaller than the sample produced without ultrasonic stirring (70 nm).

Seasonality of growth in Shanghai infants (n=4128) born in 11 consecutive years.

OBJECTIVE: To describe the seasonal growth patterns in Shanghai infants, to explore seasonal time lag between weight gain and length gain, and to investigate the long-term effect of birth season on early postnatal growth. DESIGN: Community-based longitudinal study. SETTING: Shanghai, People's Republic of China. METHOD: Children were followed up monthly from 1 to 6 months, 3 monthly from 6 to 12 months, and 6 monthly from 12 to 24 months. SUBJECTS: A total of 6018 children born between 1 January 1980 and 31 December 1990. MAIN OUTCOME MEASURES: Weight gain, length gain and change in body mass index (BMI) over the seasons of the year. RESULTS: The infants tended to grow faster in height in spring and summer, and faster in weight and BMI in autumn and winter. The seasonal effect on weight gain and length gain is largely independent. The mean length value at 1 month of age was about 2.0 cm higher in infants born in May to July than in those born in November to February. At 24 months of age this difference was reduced to about 0.7 cm. CONCLUSIONS: There is a clear and consistent seasonality in growth in Shanghai infants. The seasonality seems to act independently on weight and length. Birth month has some association with attained size, but this is reduced during the first 2 y of life.

A comparison of topical application of penciclovir 1% cream with acyclovir 3% cream for treatment of genital herpes: a randomized, double-blind, multicentre trial.

Genital herpes simplex virus (HSV) infection, a sexually transmitted disease (STD), is the commonest cause of ulcerative genital infections among the young and adult population. The significant association of genital ulceration and transmission of human immunodeficiency virus (HIV) has been shown in many studies. To explore the potential efficacy of topical treatment of genital herpes with penciclovir cream, a randomized, double-blind, multicentre, acyclovir-controlled Phase II clinical trial of penciclovir 1% cream 5 times daily up to 7 days for suppression of genital herpes was conducted in China. A total of 205 patients aged 20-59 years (mean age 36.0+/-8.8 years for acyclovir and 34.8+/-8.4 years for penciclovir) with a clinical diagnosis of genital herpes were randomly allocated to one of the 2 parallel treatment groups and used for analysis. Clinical assessment were made before treatment and followed up at every visit during the study. Our results show that there was an encouraging improvement simultaneously in the 2 groups although no significant differences in clinical efficacy with respect to clinical cure rate, and times to healing, resolution of all symptoms, absence of blisters, cessation of new blisters, crusting, and loss of crust between penciclovir and acyclovir groups in terms of primary, non-primary and total patients were found. However a significantly shorter time to crusting was found in primary penciclovir group when compared with primary acyclovir group. Adverse experience was generally infrequent and mild, and was comparable in the 2 treatment groups. Based on these preliminary clinical findings, further evaluation of penciclovir 3% cream for topical treatment of genital herpes is planned.

Secular change in growth over one decade (1980-1990) in Shanghai infants.

The aims of this study were to describe secular changes in body size in Shanghai infants, to compare the growth pattern between Shanghai children and Swedish children, and to explore the association of growth rate with parental body size, feeding practice and child health status. The study series consisted of 6,018 longitudinally followed full-term children, born between 1st January 1980 and 31st December 1990 in Fenglin Community, Shanghai. The data clearly show a positive secular trend in growth in Shanghai over the decade of observation; at 12 months, the mean increase in weight and length were 0.32 kg and 0.64 cm, and at 24 months they were 0.54 kg and 1.29 cm. The general growth pattern observed in the children in comparison with the Swedish reference was of fast growth in the first few months of life, and faltering between 9 and 24 months of age. Age at introduction of solid food, weaning age and parental body size were related to growth velocity in the first two years. There was little cumulative effect of diarrhoea on growth in the first two years of life.