Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially presents as benign fat accumulation,it may progress to steatosis,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.Mesenchymal stem cells(MSCs)are recognized for their intrinsic self-renewal,superior biocompatibility,and minimal immunogenicity,positioning them as a therapeutic innovation for liver diseases.Therefore,this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics,and support the development of MSC-based therapy in the treatment of NAFLD.

Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism

Alzheimer’s disease（AD）is a neurodegenerative disorder which is remarkably characterized by pathological hallmarks that include neurofibrillary tangles,neuronal loss extracellular senile plaques containing aggregated amyloid beta（Aβ）,and neurofibrillary tangles composed of the hyperphosphorylated form of the microtubule protein tau.It is the most common form of dementia which is characterized by severe neurodegenerative changes such as loss of neurons and synapses in brain（Kamat et al.,2014）.

Comparative Study of Disease Suppression on Various Host Plants by <i>Bacillus</i>Cyclic Lipopeptides

In biological controls using Bacillus spp., cyclic lipopeptides play a role as elicitors to induce disease resistance on various host plants. However, it is still unclear the specificity between cyclic lipopeptides and host plants to induce disease resistance. In this study, we aimed to clarify the specificity to induce disease resistance among cyclic lipopeptides on various host plants. Our data clearly showed both cyclic lipopeptides conferred disease suppression on most of host plants, but at different range of cyclic lipopeptide concentration. Our findings contribute to understanding the complex on the specificity of cyclic lipopeptide derived induced disease resistance.

Rituximab Induced Interstitial Lung Disease Diagnosis, Treatment Outcome, and Risk’s Factor, a Place for Transbronchial Pulmonary Cryobiopsy

Rituximab (RTX) is a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody, approved in late 1998 by the FDA. Effectively used as a single agent or combined with a chemotherapy regimen to treat lymphoma, RTX is a significant step forward in the arsenal treatment of idiopathic thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Side effects of RTX are commonly seen during the first infusion in up to 50% of patients and include fever, chills, and rigors. These side effects are generally transient and related to the tumor burden, probably due to a greater degree of complement activation and proinflammatory cytokine release. Severe lung toxicity like cryptogenic organizing pneumonia, pneumonitis, and interstitial lung diseases are infrequent, with most of the knowledge coming from case reports.

Glutathione-S-transferases genes-promising predictors of hepatic dysfunction

diseases pathogenesis are genes that encodes the synthesis of glutathione-Stransferase(GST),known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins,through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products.The group of GST enzymes consists of cytosolic,mitochondrial and microsomal fractions.Recently,eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known:α-,ζ-,θ-,κ-,μ-,π-,σ-,andω-.The GSTs gene family in the Human Gene Nomenclature Committee,online database recorded over 20 functional genes.The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins.Nevertheless,human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene.Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases,particularly non-alcoholic fatty liver disease,hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma.Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology,and correlations with the natural course of the diseases were subsequently postulated.

Heart Valve Injury Induced by Mediastinum Radiotherapy in Cancer Treatment

Radiotherapy as monotherapy or in combination with chemotherapy, has contributed to the drop in mortality rates related to neoplasms in the last 60 years. However, irradiation may promote heart damage and involvement is very common. As a result, VHD （valvular heart disease） is one of the earliest cardiovascular events post-radiotherapy. What it concerns to valve disease induced by chemotherapeutics, there are still only few studies. However, patients treated with chemotherapy in combination with radiotherapy had twice the risk of developing the disease when compared to those treated by radiotherapy alone. The heart injury caused by radiotherapy begins with damage to the endothelium and results in fibrosis and diffuses calcification primarily of the mitral and aortic valves. The echocardiography is the tool of choice to the patient’s assessment and follow-up after exposure. Prevention is the best option to face the valve damage induced by radiation.

Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders

Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important frontier fields in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cells in vitro and in vivo and their potential treatments of neurological disorders.

Proteomic study of three component interactions: plant, pathogens and antagonistic fungi

The molecular factors involved in the three-way interaction between plant, pathogenic fungi and antagonistic/biocontrol fungi, such as Trichoderma, are still poorly understood, even if they represent a matter of interest for improving crop management and developing new strategies for plant diseases control. The aim of this work is to investigate the components involved in this interaction and, for this purpose, a proteomic approach was used. 2-D maps of the protein extracts from the single components in various interactions between plants (potato, bean, tobacco or tomato), pathogens (Botrytis cinerea, Rhizoctonia solani or Pythium ultimum) and biocontrol fungi (Trichoderma atroviride strain P1 or Trichoderma harzianum strain T22) were obtained. The proteome of each partner was collected separately and extracted by acetone precipitation in presence of trichloroacetic acid and a reducing agent (DTT). The extracted proteins were separated by isoelectrofocusing (IEF), using IPG (Immobilized pH gradient) strips, followed by SDS-PAGE. In order to improve resolution the separations were performed both on wide than narrow pH range and on different gel lengths. Differential spots were noted in the proteome of the three-way interaction when compared to each single component. These were further characterized by mass spectrometry and in silico analysis with the aim of identifying and cloning the relative genes. During the in vitro interaction of T. harzianum strain T22 with tomato and the culture filtrate or cell walls of pathogens, the spot number was higher than in the presence of pathogen biomass. In terms of Trichoderma differential proteins displayed on 2D gels, the most important changes were obtained in the presence of P. ultimum . During the in vivo interaction with tomato, the antagonist proteome changed much more in presence of soilborne fungi R. solani and P. ultimum than with the foliar fungus B. cinerea, both in terms of total and increased or novel spots. In silico analysis of some of those spots revealed homology with intracellular enzymes (GTPases, hydrolases) and with stress-related proteins (heat shock proteins HSP70, bacteriocin cloacin). Specific proteins in the plant proteome, i.e. pathogenesis-related proteins, have been identified during the in vivo interaction of bean with R. solani and T. atroviride strain P1. This is in agreement with the demonstrated ability of these beneficial fungi to induce plant systemic disease resistance by activating expression of defence-related genes. Proteins extracted from T. atrovride strain P1 which were analysed by mass spectrometry, revealed some interesting homologies with a fungal hydrophobin of Pleurotus ostreatus and an ABC transporter of Ralstonia metallidurans. These could represent molecular factors involved in the antagonistic mechanisms of Trichoderma and play a role in the three-way interaction with the plant and other microbes.

Study on Exogenous Ethylene Induced Rice Resistance to Rhizoctonia solani

Rice sheath blight is one of the main diseases in rice production in China,which can make rice unable to absorb and utilize nutrients,and has a serious impact on rice yield and quality.In this study,exogenous ethylene was used to induce rice resistance against rice sheath blight,aiming at exploring a new environment-friendly control method of rice sheath blight.The results showed that within a range of certain concentrations,ethylene had no significant effects on mycelium growth,but it could induce resistance to sheath blight in rice.The optimum concentration was 0.2 mmol•L^(-1) and the relative control was 86.17%.It was found that ethylene could effectively increase the activities of peroxidase(POD),phenylalanine ammonia-lyase(PAL),β-1,3-glucanase and reduce the contents of malondialdehyde(MDA),which could enhance the resistance of rice against Rhizoctonia solani.In addition,qRT-PCR detected the expressions of rice defense genes,which indicated that the expressions of the POX,PAL and OsPR1b genes were up-regulated.

Epsilon-poly-L-lysine increases disease resistance of citrus against postharvest green mold by activating amino acid metabolism and phenolic comnpounds biosynthesis

As a famous fruit worldwide,citrus is susceptible to green mold caused by Penicillium digitatum,which causes large economic losses every year.e-Poly-L-lysine(e-PL)is a novel preservative with strong inhibitory effects on fungi,and has the capacity to induce disease resistance in fruit,but the mechanism has been reported rarely,especially in citrus.In the present study,8ooμg/mL e-PL and P digitatum spores were inoculated in two different wounds on the citrus pericarp at an interval of 24 h.The results revealed that e-PL inhibited that the development of green mold without direct contact with P digitatum,indicating that the disease resistance of citrus was activated.Transcriptome analysis revealed that e-PL activated amino acid metabolism and phenylpropanoid biosynthesis.Besides,the accumulation of glutamic acid,proline,arginine,serine,lysine,phenylalanine,and tyrosine were changed during storage.In phenylpropanoid biosynthesis,-PL increased phenylalanine ammonia-lyase(PAL),cinnamate 4-hydroxylase(C4H),and 4-coumarate:coenzyme A ligase(4CL)activities and total phenolic and flavonoid contents.Importantly.among these phenolic compounds,e-PL promoted the accumulation of individual phenolic compounds including ferulic acid,chlorogenic acid,p-coumaric acid,caffeic acid,gallic acid,catechins,epicatechin,and narirutin.In conclusion,e-PL enhanced the resistance of citrus through amino acid metabolism and accumulation of phenolic compounds.These results improved the knowledge of the mechanism of-PL-induced disease resistance and provided a fresh theoretical basis for the use of e-PL in postharvest citrus preservation.

TWO TYPES OF CONDITION FOR THE GLOBAL STABILITY OF DELAYED SIS EPIDEMIC MODELS WITH NONLINEAR BIRTH RATE AND DISEASE INDUCED DEATH RATE

We study global asymptotic stability for an SIS epidemic model with maturation delay proposed by K. Cooke, P. van den Driessche and X. Zou, Interaction of maturation delay and nonlinear birth in population and epidemic models, J. Math. Biol. 39（4） （1999） 332-352. It is assumed that the population has a nonlinear birth term and disease causes death of infective individuals. By using a monotone iterative method, we establish sufficient conditions for the global stability of an endemic equilibrium when it exists dependently on the monotone property of the birth rate function. Based on the analysis, we further study the model with two specific birth rate functions BI（N） = be-aN and B3（N） = A/N ＋ c, where N denotes the total population. For each model, we obtain the disease induced death rate which guarantees the global stability of the endemic equilibrium and this gives a positive answer for an open problem by X. Q. Zhao and X. Zou, Threshold dynamics in a delayed SIS epidemic model, J. Math. Anal. Appl. 257（2） （2001） 282-291.

Antiviral Abidol is Associated with the Reduction of In-Hospital Mortality in COVID-19 Patients

Objective:Coronavirus disease 2019(COVID-19)is a global public health crisis.There are no specific antiviral agents for the treatment of SARS-CoV-2.Information regarding the effect of Abidol on in-hospital mortality is scarce.The present study aimed to evaluate the treatment effect of Abidol for patients with COVID-19 before and after propensity score matching(PSM).Methods:This retrospective cohort study analyzed 1019 patients with confirmed COVID-19 in China from December 22,2019 to March 13,2020.Patients were divided to Abidol(200mg,tid,5-7days,n=788,77.3%)and No-Abidol(n=231,22.7%)groups.The primary outcome was the mortality during hospitalization.Results:Among 1019 COVID-19 patients,the age was(60.4±14.5)years.Abidol-treated patients,compared with No-Abidoltreated patients,had a shorter duration from onset of symptoms to admission,less frequent renal dysfunction,lower white blood cell counts(lymphocytes<0.8)and erythrocyte sending rate,lower interleukin-6,higher platelet counts and plasma IgG and oxygen saturation,and less frequent myocardial injury.The mortality during hospitalization before PSM was 17.9% in Abidol group and 34.6% in No-Abidol(hazard ratio(HR)=2.610,95% confident interval(CI):1.980–3.440),all seen in severe and critical patients.After PSM,the in-hospital death was 13.6% in Abidol and 28.6% in No-Abidol group(HR=2.728,95%CI:1.598–4.659).Conclusions:Abidol-treatment results in less in-hospital death for severe and critical patients with COVID-19.Further randomized study is warranted to confirm the findings from this study.

Molecular Basis of Transfer of Induced Resistance in Plants

Two brown spot disease resistant varieties of tobacco, named NC89 V1 and NC89 V2, were obtained by first inducing from disease sensitive NC89 with the two hypovirulent viruses ToMV N14 and CMV SV52, then tissue culturing the plants and finally seed breeding. The disease resistance for both varieties was verified to be stable in three generations. The transcription activities of five plant defense response genes, pr 1a, chi, chs, pal, and lox, in NC89, NC89 V1, and NC89 V2 were studied through RNA blot hybridization. Genome DNA structural differences among the three tobacco lines were identified using randomly amplified polymorphic DNA(RAPD).