Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

NECAB family of neuronal calcium-binding proteins in health and disease

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.

In vivo and in vitro study of resorbable magnesium wires for medical implants:Mg purity,surface quality,Zn alloying and polymer coating

Magnesium is an excellent material in terms of biocompatibility and its corrosion products can serve as an active source for new bone formation.However,localized corrosion and H_(2)generation limit the potential of Mg-based implants.Utilizing low-alloyed Mg-Zn wires can strongly reduce problems with large H_(2)bubbles and improve the mechanical properties considerably while maintaining excellent long-term biocompatibility.Acidic pickling and a polymer coating can be effectively used to lower the rate of in vivo degradation.In this work,microstructural,mechanical,and in vitro characterization of 250μm and 300μm extruded wires made from ultra-pure Mg,commercially pure Mg,Mg-0.15Zn,Mg-0.4Zn and Mg-1Zn was performed.Additionally,Mg-0.4Zn wires together with a variant coated with a copolymer of L-lactide andε-caprolactone were tested in vivo on artificially damaged Wistar rat femurs.Based on the observed Mg-induced osteogenesis,polymer-coated Mg wires with a small addition of Zn are a perspective material for bone-support applications,such as cerclage and fixation wires.

Delineation of biomarkers and molecular pathways of residual effects of fluoxetine treatment in juvenile rhesus monkeys by proteomic profiling

Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective serotonin reuptake inhibitor,the possible long-term effects of fluoxetine on brain development in children are poorly understood.In the current study,we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques(Macaca mulatta)one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex(DLPFC)and cingulate cortex(CC)that correlated with impulsivity in animals,suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment.Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.

Pointing fingers at blood contact:mechanisms of subventricular zone neural stem cell differentiation

The limited ability of the central nervous system(CNS)to regenerate in adult mammals after injury or disease is a significant problem.Intriguingly,neural stem/progenitor cells(NSPCs)offer great promise for regenerating the CNS.Endogenous or transplanted NSPCs contribute to repair processes,but their differentiation and function are abnormal in CNS injury and disease.The main reasons for these abnormalities are changes in the extracellular environment in the injured CNS that affect signaling pathways and transcriptional regulation in NSPCs.

Dysregulated expression and distribution of Kif5αin neurites of wobbler motor neurons

Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis(ALS)and in animal models,suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS.Dysregulation of Kinesin-family-member 5α(Kif5α),a neuron-specific isoform of heavy chain kinesin family,has been described in several neurological disorders,in humans and animal models,including ALS.In this study,we determined Kif5αexpression by gene sequencing,quantitative reverse transcription-polymerase chain reaction,and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn.Further,we observed the distribution of Kif5αand mitochondria along motor neuronal branches by confocal imaging.Our results showed that Kif5αexpression was greatly dysregulated in wobbler mice,which resulted in altered distribution of Kif5αalong motor neuronal branches with an abnormal mitochondrial distribution.Thus,our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level,like misallocation of cytoskeletal proteins or organelles like mitochondria.

The role of mesenchymal stem cell-derived exosomes in tumor progression

Exosomes derived from mesenchymal stem cells(MSC-Exos)are nano-sized extracellular vesicles enriched with bioactive molecules,such as microRNAs,enzymes,cytokines,chemokines,immunomodulatory,trophic,and growth factors.These molecules regulate the survival,phenotype,and function of malignant and tumor-infiltrated immune cells.Due to their nano-size and bilayer lipid envelope,MSC-Exos can easily bypass biological barriers and may serve as drug carriers to deliver chemotherapeutics directly into the tumor cells.Here,we summarize current knowledge regarding molecular mechanisms responsible for MSC-Exos-dependent modulation of tumor progression and discuss insights regarding the therapeutic potential of MSC-Exos in the treatment of malignant diseases.

The Effects of Using a Specially Designed Stirrup on Kinetic Energy Absorption by the Knee Joint of 12 Show Jumping/Eventing Riders

The use of Winderen Knee Protection Solution stirrups compared to standard iron stirrups, reveals the following benefits: 1) A reduction of stress or strain time in the order of 14 seconds per minute of activity whilst walking and 5 - 7 seconds less whilst trotting or cantering for muscles around the knee. 2) A reduction of stress or strain time in the order of 25 seconds per minute of activity whilst walking and 9 - 10 seconds less whilst trotting or cantering for ligaments around the knee. 3) A significant improvement in the E-score (less time exposed to stress and shock) and ST-score (lower force around the knee) whilst walking. 4) A considerable improvement in rider comfort and feeling of leg stability (self-assessment) compared with the owners current stirrups, whilst riding.

小鼠cofilin-1基因及其真核表达载体的构建与体内外表达

【目的】构建能够在神经系统中高效表达的小鼠cofilin-1野生型(Cfl1-wt)、活化型(Cfl1-S3A)、失活型(Cfl1-S3D)3种真核表达载体,并研究其在鸡胚脊髓神经元中的表达情况,为进一步探讨cofilin-1在大脑发育过程中对神经元迁移的影响奠定基础。【方法】从成年小鼠大脑组织中提取RNA,经反转录获得cDNA样本,RT-PCR扩增小鼠cofilin-1基因的CDS区,经引物设计引入点突变,扩增了野生型、活化型及失活型的cofilin-1基因片段,克隆入pCAG-MCS-myc真核表达载体中。经双酶切和测序鉴定后,转染CHO细胞,通过半定量RT-PCR和免疫荧光染色检测其在细胞中的表达情况。利用鸡胚活体原位电转的方法,将重组质粒转染胚胎发育第3天(E3)的鸡胚脊髓,在胚胎发育第6天(E6)取材,切片后经免疫荧光染色观察并统计分析重组质粒在脊髓中的表达情况。【结果】克隆并模拟了小鼠cofilin-1野生型、活化型和失活型的cDNA片段,成功构建了pCAG-cfl1-wt、pCAG-cfl1-S3A和pCAGcfl1-S3D3种真核表达载体。体外转染CHO细胞,半定量RT-PCR检测及统计学分析表明,转染重组质粒的CHO细胞中,Cofilin-1mRNA相对表达量与对照组(未转染质粒的正常CHO细胞)存在显著性差异;免疫荧光染色后观察到了Cofilin-1融合蛋白的表达。对经活体原位电转转染重组质粒的鸡胚脊髓切片进行免疫荧光染色,检测到Cofilin-1融合蛋白的表达,且重组质粒转染效果与pCAG-EGFP转染效果无明显差异。【结论】pCAG-cfl1-wt、pCAGcfl1-S3A和pCAG-cfl1-S3D3种真核表达载体的成功构建及其在体内外的高效表达,为进一步研究cofilin-1及其Ser3位点的磷酸化在神经元迁移中的作用机制奠定了基础。

Oxidative stress: the lowest common denominator of multiple diseases

Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life forms. However, cells that benefit from oxidative respiration also suffer from reactive oxygen species because they adapted to oxygen as an energy source. Healthy cells balance the formation and elimination of reactive oxygen species thereby creating and keeping reactive oxygen species-homeostasis. When the concentration of free radicals exceeds a critical level and homeostasis is disturbed, oxidative stress occurs leading to damage of multiple cellular molecules and compartments. Therefore, oxidative stress plays an important role in the physiology and pathology of various diseases. Often, the antioxidant protection system becomes pathologically unbalanced in the genesis of several diseases, leading to functional losses of the organism, as in the case of amyotrophic lateral sclerosis, or cells develop metabolic mechanisms to use this system as protection against external influences, such as in the case of glioblastoma cells. Either way, understanding the underlying deregulated mechanisms of the oxidative protection system would allow the development of novel treatment strategies for various diseases. Thus, regardless of the direction in which the reactive oxygen species-homeostasis disequilibrate, the focus should be on the oxidative protection system.

Psychiatric comorbidity in the treatment of patients with inflammatory bowel disease

Ulcerative colitis and Crohn’s disease, commonly known as inflammatory bowel disease (IBD), draw attention from specialists of various disorders, including gastroenterology, psychiatry, and radiology. The involvement of a cortical influence in the brain-gut axis as well as the interaction of the hypothalamic-pituitary-adrenal axis and the peripheral nervous system provide an initial explanation of the psychological symptoms associated with IBD. The involvement of structures the limbic system, such as the anterior cingulate cortex, the prefrontal cortex, and the amygdala, paves the way for the discovery of the mechanisms underlying depression depression, anxiety, alexithymia, personality traits, and other psychological impairments following the onset of IBD. Psychiatric therapy in IBD patients is almost as important as the gastroenterological approach and consists of pharmacological treatment and psychotherapy. Neither of the available psychiatric treatment methods is considered the golden standard because both methods have side effects, and psychotropic medication can provoke the worsening of IBD symptoms. Thus, both approaches must be applied with awareness of the possibility of side effects. We suggest that psychiatrists and gastroenterologists work together to reach a consensus on IBD therapy to ensure success and to reduce side effects and relapse to the lowest possible rates.

Depression and anxiety levels in therapy-nave patients with inflammatory bowel disease and cancer of the colon

AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa including 20 males and 10 females, aged 39-78, underwent a structured interview, which comprised Hamilton’s Depression Rating Inventory, Hamilton’s Anxiety Rating Inventory and Paykel’s Stressful Events Rating Scale. RESULTS: Patients of the IBD group expressed both depression and anxiety. Depressive mood, sense of guilt, psychomotor retardation and somatic anxiety were also more pronounced in IBD patients. The discriminant function analysis revealed the total depressive score was of high importance for the classification of a newly diagnosed patient into one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher levels of depression and anxiety. Moreover, a psychiatrist in the treatment team is advisable from the beginning.

Comparison of two nutritional assessment methods in gastroenterology patients

AIM:To investigate and compare efficacy and differences in the nutritional status evaluation of gastroenterology patients by application of two methods:subjective global assessment(SGA) and nutritional risk index(NRI).METHODS:The investigation was performed on 299 hospitalized patients,aged 18-84 years(average life span 55.57 ± 12.84),with different gastrointe-stinal pathology,admitted to the Department of Gastroenterohepatology,Clinical and Hospital Center "Bezanijska Kosa" during a period of 180 d.All the patients,after being informed in detail about the study and signing a written consent,underwent nutritional status analysis,which included two different nutritional indices:SGA and NRI,anthropometric parameters,bioelectrical impedance analysis,and biochemical markers,within 24 h of admission.RESULTS:In our sample of 299 hospitalized patients,global malnutrition prevalence upon admission varied from 45.7% as assessed by the SGA to 63.9% by NRI.Two applied methods required different parameters for an adequate approach:glucose level(5.68 ± 1.06 mmol/L vs 4.83 ± 1.14 mmol/L,F = 10.63,P = 0.001);body mass index(26.03 ± 4.53 kg/m2 vs 18.17 ± 1.52 kg/m2,F = 58.36,P < 0.001);total body water(42.62 ± 7.98 kg vs 36.22 ± 9.32 kg,F = 7.95,P = 0.005);basal metabolic rate(1625.14 ± 304.91 kcal vs 1344.62 ± 219.08 kcal,F = 9.06,P = 0.003) were very important for SGA,and lymphocyte count was relevant for NRI:25.56% ± 8.94% vs 21.77% ± 10.08%,F = 11.55,P = 0.001.The number of malnourished patients rose with the length of hospital stay according to both nutritional indices.The discriminative function analysis(DFA) delineated the following parameters as important for prediction of nutritional status according to SGA assessment:concentration of albumins,level of proteins,SGA score and body weight.The DFA extracted MAMC,glucose level and NRI scores were variables of importance for the prediction of whether admitted patients would be classif ied as well or malnourished.CONCLUSION:SGA showed higher sensitivity to predictor factors.Assessment of nutritional status requires a multidimensional approach,which includes different clinical indices and various nutritional param eters.

Downregulation of thioredoxin reductase 1 expression in the substantia nigra pars compacta of Parkinson's disease mice

Because neurons are susceptible to oxidative damage and thioredoxin reductase 1 is extensively distributed in the central nervous system and has antioxidant properties, we speculated that the enzyme may be involved in the pathogenesis of Parkinson＇s disease. A Parkinson＇s disease model was produced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into C57BL/6 mice. Real-time reverse transcription-PCR, western blot analysis and colorimetric assay showed that the levels of thioredoxin reductase 1 mRNA and protein were decreased, along with a significant reduction in thioredoxin reductase activity, in the midbrain of Parkinson＇s disease mice compared with normal mice. Immunohistochemical staining revealed that the number of thioredoxin reductase 1-positive neurons in the substantia nigra pars compacta of Parkinson＇s disease mice was significantly decreased compared with normal mice. These experimental findings suggest that the expression of thioredoxin reductase 1 in the substantia nigra pars compacta of Parkinson＇s disease mice is significantly decreased, and that the enzyme may be associated with disease onset.

Improved guided bone regeneration by combined application of unmodified, fresh autologous adipose derived regenerative cells and plasma rich in growth factors:A first-in-human case report and literature review

BACKGROUND Novel strategies are needed for improving guided bone regeneration(GBR) in oral surgery prior to implant placement, particularly in maxillary sinus augmentation(GBR-MSA) and in lateral alveolar ridge augmentation(LRA). This study tested the hypothesis that the combination of freshly isolated, unmodified autologous adipose-derived regenerative cells(UA-ADRCs), fraction 2 of plasma rich in growth factors(PRGF-2) and an osteoinductive scaffold(OIS)(UAADRC/PRGF-2/OIS) is superior to the combination of PRGF-2 and the same OIS alone(PRGF-2/OIS) in GBR-MSA/LRA.CASE SUMMARY A 79-year-old patient was treated with a bilateral external sinus lift procedure as well as a bilateral lateral alveolar ridge augmentation. GBR-MSA/LRA was performed with UA-ADRC/PRGF-2/OIS on the right side, and with PRGF-2/OIS on the left side. Biopsies were collected at 6 wk and 34 wk after GBRMSA/LRA. At the latter time point implants were placed. Radiographs(32 mo follow-up time) demonstrated excellent bone healing. No radiological or histological signs of inflammation were observed. Detailed histologic,histomorphometric, and immunohistochemical analysis of the biopsies evidenced that UA-ADRC/PRGF-2/OIS resulted in better and faster bone regeneration than PRGF-2/OIS.CONCLUSION GBR-MSA with UA-ADRCs, PRGF-2, and an OIS shows effectiveness without adverse effects.

Enhancement of insulin-producing cell differentiation from embryonic stem cells using pax4-nucleofection method

AIM： To enhance the differentiation of insulin producing cell （IPC） ability from embryonic stem （ES） cells in vitro. METHODS： Four-day embryoid body （EB）-formatted ES cells were dissociated as single cells for the followed plasmid DNA delivery. The use of NucleofectorTM electroporator （Amaxa biosystems, Germany） in combination with medium-contained G418 provided a high efficiency of gene delivery for advanced selection. Neucleofected cells were plated on the top of fibronectincoated Petri dishes. Addition of Ly294002 and raised the glucose in medium at 24 h before examination.The differentiation status of these cells was monitored by semi-quantitative PCR （SQ-PCR） detection of the expression of relative genes, such as oct-4, sox-17, foxa2, mixll, pdx-1, insulin 1, glucagons and somatostatin. The percentage of IPC population on d 18 of the experiment was investigated by immunohistochemistry （IHC）, and the content/secretion of insulin was estimated by ELISA assay. The mice with severe combined immunodeficiency disease （SCID） pretreated with streptozotocin （STZ） were used to eliminate plasma glucose restoration after pax4^＋ ES implantation. RESULTS： A high efficiency of gene delivery was demonstrated when neucleofection was used in the present study; approximately 70% cells showed DsRed expression 2 d after neucleofection. By selection of medium-contained G418, the percentage of DsRed expressing cells kept high till the end of study. The pancreatic differentiation seemed to be accelerated by pax4 nucleofection. When compared to the group of cells with mock control, foxa2, mixll, pdxl, higher insulin and somatostatin levels were detected by SQ-PCR 4 d after nucleofection in the group of pax4 expressing plasmid delivery. Approximately 55% of neucleofected cells showed insulin expression 18 d after neucleofection, and only 18% of cells showed insulin expression in mock control. The disturbance was shown by nucleofected pax4 RNAi vector; only 8% of cells expressed insulin 18 d after nucleofection. A higher IPC population was also detected in the insulin content by ELISA assay, and the glucose dependency was demonstrated in insulin secretion level. In the animal model, improvement of average plasma glucose concentration was observed in the group of pax-4 expressed ES of SCID mice pretreated with STZ, but no significant difference was observed in the group of STZ-pretreated SCID mice who were transplanted ES with mock plasmid. CONCLUSION： Enhancement of IPC differentiation from EB-dissociated ES cells can be revealed by simply using pax4 expressing plasrnid delivery. Not only more IPCs but also pancreatic differentiation-related genes can be detected by SQ-PCR. Expression of relative genes, such as foxa 2, mixl 1, pdx-1, insulin 1 and somatostatin after nucleofection, suggests that pax4 accelerates the whole differentiation progress. The higher insulin production with glucose dependent modulation suggests that pax4 expression can drive more mature IPCs. Although further determination of the entire mechanism is required, the potential of pax-4-nucleofected cells in medical treatment is promising.

Characterization of pancreatic stem cells derived from adult human pancreas ducts by fluorescence activated cell sorting

AIM： To isolate putative pancreatic stem cells （PSCs） from human adult tissues of pancreas duct using serumfree, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of β-cell differentiation in these PSCs were evaluated as well. METHODS： By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The MatrigelTM was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting （FACS） was used to detect the phenotypic markers of putative PSCs. RESULTS： A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin. They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29, CD44, CD49, CD50, CD51, CD62E, PDGFR-α, CD73 （SH2）, CD81, CD105（SH3）. CONCLUSION： In this study, we successfully isolated PSCs from adult human pancreatic duct by using serumfree medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.

Therapeutic potential of mesenchymal stem cells in the treatment of acute liver failure

Acute liver failure(ALF)is a severe and life-threatening condition in which rapid deterioration of liver function develops in a patient who has no preexisting liver disease.Mesenchymal stem cells(MSCs)are immunoregulatory stem cells which are able to modulate phenotype and function of all immune cells that play pathogenic role in the development and progression of ALF.MSCs in juxtacrine and paracrine manner attenuate antigen-presenting properties of dendritic cells and macrophages,reduce production of inflammatory cytokines in T lymphocytes,suppress hepatotoxicity of natural killer T(NKT)cells and promote generation and expansion of immunosuppressive T,B and NKT regulatory cells in acutely inflamed liver.Due to their nano-sized dimension and lipid envelope,intravenously injected MSC-derived exosomes(MSC-Exos)may by-pass all biological barriers to deliver MSC-sourced immunoregulatoy factors directly into the liver-infiltrated immune cells and injured hepatocytes.Results obtained by us and others revealed that intravenous administration of MSCs and MSC-Exos efficiently attenuated detrimental immune response and acute inflammation in the liver,suggesting that MSCs and MSC-Exos could be considered as potentially new remedies in the immunotherapy of ALF.In this review,we emphasize the current knowledge about molecular and cellular mechanisms which are responsible for MSC-based modulation of liver-infiltrated immune cells and we discuss different insights regarding the therapeutic potential of MSCs in liver regeneration.

Adult neural stem cell dysfunction in the subventricular zone of the lateral ventricle leads to diabetic olfactory defects

Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.

Carcinosarcoma of the stomach:A case report and review of the literature

Carcinosarcomas are rare,malignant,biphasic tumors. We report the case of a 62-year-old man with gastric carcinosarcoma,along with its clinical,macroscopic and histopathological features. Macroscopically,a specimen of deformed stomach was obtained that measured 200 mm×150 mm×100 mm. A 150 mm×100 mm× 50 mm exophytic tumoral mass (Borrmann typeⅠ) was found,which involved the posterior wall from the cardia to the antrum. Histopathologically,a mixed type of malignancy was revealed: an adenocarcinoma with intestinal metaplasia,with interposed fascicles of fusiform atypical cells and numerous large,rounded and oval cells. The tumor showed positive histochemistry for cytokeratin 18,epithelial membrane antigen,carcinoembryonic antigen,chromogranin A and vimentin. Liver metastases were diagnosed 8 mo postoperatively,and the patient died 4 mo later. A review of the available literature is also presented.