Neurotransmitters regulateβcells insulin secretion:A neglected factor

βcells are the main cells responsible for the hypoglycemic function of pancreatic islets,and the insulin secreted by these cells is the only hormone that lowers blood glucose levels in the human body.βcells are regulated by various factors,among which neurotransmitters make an important contribution.This paper discusses the effects of neurotransmitters secreted by various sympathetic and parasympathetic nerves onβcells and summarizes the mechanisms by which various neurotransmitters regulate insulin secretion.Many neurotransmitters do not have a single source and are not only released from nerve terminals but also synthesized byβcells themselves,allowing them to synergistically regulate insulin secretion.Almost all of these neurotransmitters depend on the presence of glucose to function,and their actions are mostly related to the Ca^(2+)and cAMP concentrations.Although neurotransmitters have been extensively studied,many of their mechanisms remain unclear and require further exploration by researchers.

Experiment on inducing apoptosis of melanoma cells by micro-plasma jet

As a promising cancer treatment method,cold atmospheric plasma has received widespread attention in recent years.However,previous research has focused more on how to realize and expand the anti-cancer scope of plasma jet.There are also studies on the killing of small-scale cancer cells,but the effects of plasma jet on normal cells and normal cell clusters have been ignored.Therefore,we proposed a 50μm sized micro-plasma jet device,and used the device to treat melanoma cells(A-375)and human glial cells(HA1800)to evaluate their anti-cancer effects and effects on normal cells.The experimental results show that this kind of micro-plasma jet device can effectively inactivate cancer cells in a short period of time,while having little effect on normal cells.This work provides a certain experimental basis for the application offine plasma jet to clinically inactivate cancer cells.

Anti-diabetic effects of Caulerpa lentillifera:stimulation of insulin secretion in pancreatic β-cells and enhancement of glucose uptake in adipocytes

Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free system.Then,interleukin-1βand interferon-γinduced cell death and insulin secretion were measured in rat insulinoma(RIN)cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA kit,respectively.Glucose uptake and glucose transporter expression were measured by fluorometry and western blotting,using 3T3-Ll adipocytes.Results:C.lentillifera extract significantly decreased dipeptidyl peptidase-IV and a-glucosidase enzyme activities,and effectively inhibited cell death and iNOS expression in interleukin-1βand interfcron-γinduced RIK cells.Furthermore,C.lntillifera extract significantly enhanced insulin secretion in RTN cells and glucose transporter expression and glucose uptake in 3T3-L1adipocytes.Conclusions:Thus,our results suggest that C.lentillifera could be used as a potential antidiabetic agenl.

Effects of glycine on phagocytosis and secretion by Kupffer cells in vitro

AIM:To investigate the effects and mechanisms of action of glycine on phagocytosis and tumor necrosis factor(TNF)-α secretion by Kupffer cells in vitro. METHODS:Kupffer cells were isolated from normal rats by collagenase digestion and Percoll density gradient differential centrifugation.After culture for 24 h,Kupffer cells were incubated in fresh Dulbecco's Modification of Eagle's Medium containing glycine (G1:1 mmol/L,G2:10 mmol/L,G3:100 mmol/L and G4:300 mmol/L)for 3 h,then used to measure phagocytosis by a bead test,TNF-α secretion after lipopolysaccharide stimulation by radioactive immunoassay,and microfilament and microtubule expression by staining with phalloidin-fluorescein isothiocyanate (FITC)or a monoclonal anti-α tubulin-FITC antibody, respectively,and evaluated under a ultraviolet fluorescence microscope. RESULTS:Glycine decreased the phagocytosis of Kupffer cells at both 30 min and 60 min(P<0.01,P< 0.05).The numbers of beads phagocytosed by Kupffer cells in 30 min were 16.9±4.0(control),9.6±4.1(G1), 12.1±5.7(G2),8.1±3.2(G3)and 7.5±2.0(G4),and were 22.5±7.9(control),20.1±5.8(G1),19.3±4.8 (G2),13.5±4.7(G3)and 9.2±3.1(G4)after 60 min. TNF-α secretion by Kupffer cells in G1(0.19±0.03),G2 (0.16±0.04),G3(0.14±0.03)and G4(0.13±0.05) was significantly less than that in controls(0.26±0.03, P<0.01),and the decrease in secretion was dose-dependent(P<0.05).Microfilaments of Kupffer cells in G2, G3 and G4 groups were arranged in a disorderly manner. The fluorescence densities of microtubules in G1(53.4± 10.5),G2(54.1±14.6),G3(64.9±12.1)and G4(52.1 ±14.2)were all lower than those in the controls(102.2 ±23.7,P<0.01),but the decrease in microtubule fluorescence density was not dose-dependant. CONCLUSION:Glycine can decrease the phagocytosis and secretion by Kupffer cells in vitro,which may be related to the changes in the expression of microfilaments and microtubules induced by Kupffer cells.

Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca2+ and cyclic adenosine monophosphate levels through PI3K/AKT pathway

BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.

Separate basolateral and apical phosphatidylcholine secretion routes in intestinally differentiated tumor cells

AIM:To investigate whether the secretion of phospha-tidylcholine(PC)in intestinal mucus occurs by apical secretion or via basolateral excretion and to determine its subsequent passage across the tight junctions to the apical mucus.METHODS:We addressed this question using the po-larized intestinally differentiated tumor cell line CaCo-2 grown on filters to confluence in Transwell culture chambers.The released PC and sphingomyelin(Sph)from apical and basolateral media were analyzed by mass spectrometry.RESULTS:The secreted PC species were identical in both compartments indicating the same intracellular origin of PC.However,PC secretion into the basolateral compart-ment was more effective,and the PC:Sph ratio in the ba-solateral compartment was signif icantly higher than that in the apical compartment(8.18 ± 1.84 vs 4.31 ± 1.22,P = 0.01).Both pathways were temperature sensitive and were unaltered in the presence of cyclosporine.CONCLUSION:The data demonstrate the PC secre-tion capacity of CaCo-2 cells and indicate two sepa-rated apical and basolateral release mechanisms.

A Review on the Biological Characteristics and Secretory Functions of Adipose-derived Mesenchymal Stem Cells

Adipose-derived mesenchymal stem cells （ADSCs） can be largely and easily obtained from a wide range of sources. Moreover, they have self-renewal ability, multi-differentiation potential, and an important role in immune regulation. They can secrete a variety of cytokines to regulate the in vivo micro-environment. Therefore, ADSCs are the ideal seed ceils for stem ceils application. This paper reviews the location, isolation, surface markers, proliferation, differentiation and other biological characteristics of ADSCs, as well as their secretory function and relative researches. ADSCs are expected to become excellent seed cells for cell therapy and tissue engineering through in-depth studies.

Microgels for Cell Delivery in Tissue Engineering and Regenerative Medicine

Microgels prepared from natural or synthetic hydrogel materials have aroused extensive attention as multifunctional cells or drug carriers,that are promising for tissue engineering and regenerative medicine.Microgels can also be aggregated into microporous scaffolds,promoting cell infiltration and proliferation for tissue repair.This review gives an overview of recent developments in the fabrication techniques and applications of microgels.A series of conventional and novel strategies including emulsification,microfluidic,lithography,electrospray,centrifugation,gas-shearing,three-dimensional bioprinting,etc.are discussed in depth.The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy.Additionally,we expound on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering.Through stimulating innovative ideas,the present review paves new avenues for expanding the application of microgels in cell delivery techniques.

MACS-W:A modified optical clearing agent for imaging 3D cell cultures

Three-dimensional(3D)cell cultures have contributed to a variety of biological research fields by filling the gap between monolayers and animal models.The modern optical sectioning microscopic methods make it possible to probe the complexity of 3D cell cultures but are limited by the inherent opaqueness.While tissue optical clearing methods have emerged as powerful tools for investigating whole-mount tissues in 3D,they often have limitations,such as being too harsh for fragile 3D cell cultures,requiring complex handling protocols,or inducing tissue deformation with shrinkage or expansion.To address this issue,we proposed a modified optical clearing method for 3D cell cultures,called MACS-W,which is simple,highly efficient,and morphology-preserving.In our evaluation of MACS-W,we found that it exhibits excellent clearing capability in just 10 min,with minimal deformation,and helps drug evaluation on tumor spheroids.In summary,MACS-W is a fast,minimally-deformative and fluorescence compatible clearing method that has the potential to be widely used in the studies of 3D cell cultures.

Immune evasion and therapeutic opportunities based on natural killer cells

Natural killer(NK)cells can elicit an immune response against malignantly transformed cells without recognizing antigens,and they also exhibit cytotoxic effects and immune surveillance functions in tumor immunotherapy.Although several studies have shown the promising antitumor effects of NK cells in immunotherapy,their function is often limited in the tumor microenvironment because tumor cells can easily escape NK cell-induced death.Thus,for efficient tumor immunotherapy,the mechanism by which tumor cells escape NK cell-induced cytotoxicity must be fully understood.Various novel molecules and checkpoint receptors that mediate the disruption of NK cells in the tumor microenvironment have been discovered.In this review,we analyze and detail the major activating and inhibitory receptors on the surface of NK cells to delineate the mechanism by which tumor cells suppress NKG2D ligand expression and increase tumor receptor and inhibitory receptor expression[NKG2A,programmed cell death1(PD-1),and T-cell immunoglobulin and immunoreceptor tyrosine inhibitory motif(TIGIT)]on the NK cell surface,and thus inhibit NK cell activity.We also reviewed the current status of treatments based on these surface molecules.By comparing the therapeutic effects related to the treatment status and bypass mechanisms,we attempt to identify optimal single or combined treatments to suggest new treatment strategies for tumor immunotherapy.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury

There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Toward high-efficiency perovskite solar cells with one-dimensional oriented nanostructured electron transport materials

The unique advantages of one-dimensional(1D)oriented nanostructures in light-trapping and chargetransport make them competitive candidates in photovoltaic(PV)devices.Since the emergence of perovskite solar cells(PSCs),1D nanostructured electron transport materials(ETMs)have drawn tremendous interest.However,the power conversion efficiencies(PCEs)of these devices have always significantly lagged behind their mesoscopic and planar counterparts.High-efficiency PSCs with 1D ETMs showing efficiency over 22%were just realized in the most recent studies.It yet lacks a comprehensive review covering the development of 1D ETMs and their application in PSCs.We hence timely summarize the advances in 1D ETMs-based solar cells,emphasizing on the fundamental and optimization issues of charge separation and collection ability,and their influence on PV performance.After sketching the classification and requirements for high-efficiency 1D nanostructured solar cells,we highlight the applicability of 1D TiO_(2)nanostructures in PSCs,including nanotubes,nanorods,nanocones,and nanopyramids,and carefully analyze how the electrostatic field affects cell performance.Other kinds of oriented nanostructures,e.g.,ZnO and SnO_(2)ETMs,are also described.Finally,we discuss the challenges and propose some potential strategies to further boost device performance.This review provides a broad range of valuable work in this fast-developing field,which we hope will stimulate research enthusiasm to push PSCs to an unprecedented level.

Influence of Hemoglobin S Haplotypes on the Responses to Hydroxyurea Treatment in Children with Sickle Cell Disease in Abidjan, Côte d’Ivoire

Background: In Côte d’Ivoire so far, the circulating haplotypes have been inferred on the phenotypic profiling of SCD patients. The impact of the circulating haplotypes on the use of Hydroxyurea has not been assessed yet. Therefore the objective of this study is to identify in Abidjan the HbS haplotypes that modulate HU treatment responses. Methods: In a cross-sectional descriptive and analytical study, children aged 5 to 15 years with SCD, and carrying the hemoglobin phenotypes SSFA2 and SFA2, were recruited into a HU treatment cohort. Various parameters on the haplotypes and the outcomes of the treatment were analyzed. Results: Thirty nine children with SCD were included. The phenotypic profile of the cohort was 86.6% of SSFA2 and 15.4% of SFA2. Three haplotypes were found, the Benin haplotype, the Senegal haplotype, and an atypical one. The participants belonged to three genotypes, Benin/atypical (64.1%), Benin/Senegal (33.3%) and Senegal/Senegal (2.6%). Overall, HU treatment was successful in all haplotypes with 12 out of 39 patients failing treatment after 12 months in the Benin haplotype group. The association between HU treatment success and the Benin haplotype was found in terms of the decrease in the number of white blood cells and the students missing class. Conclusion: The study revealed that inferring haplotype based on the phenotypic profile could be inaccurate. The proportion of atypical haplotype that were not previously described in Côte d’Ivoire was high. All the haplotypes seemed to be associated with HU treatment success but some patients with Benin haplotype did not respond well.

Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells:Potential implications for their clinical use

Mesenchymal stromal/stem cells(MSCs)have shown significant therapeutic potential,and have therefore been extensively investigated in preclinical studies of regenerative medicine.However,while MSCs have been shown to be safe as a cellular treatment,they have usually been therapeutically ineffective in human diseases.In fact,in many clinical trials it has been shown that MSCs have moderate or poor efficacy.This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs.Recently,specific priming strategies have been used to improve the therapeutic properties of MSCs.In this review,we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs.We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes.Particularly,while hypoxic priming can be used primarily for the treatment of acute diseases,inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders.The shift in approach from regeneration to inflammation implies,in MSCs,a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways.The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.

Psychological Experience of Mothers of Children with Sickle Cell Disease Followed at the Pediatric Department of Bouaké University Teaching Hospital

Introduction: Sickle cell disease has physical and emotional repercussions on the child and his family. The aim of this study was to describe the psychosocial experiences of mothers of children with sickle cell disease in order to improve the overall care of the child. Methods: This was a descriptive cross-sectional study carried out in the pediatrics department of Bouaké University Teaching Hospital from June to September 2023. It focused on mothers of major sickle-cell-affected children followed up in the pediatrics department of the Bouaké University Teaching Hospital. The variables studied were sociodemographic, psychological, social and economic. Results: Of the 40 mothers surveyed, 15% were not in school and 32.5% were unemployed. For them, sickle cell disease was of natural (genetic) origin in 90% and supernatural in 10%. They stated that the child had an average age of 36 months (extremes 7 and 108 months) when the disease was discovered. And 52% of them were satisfied with the way the disease was clearly and completely announced. Following the announcement, the questioned mothers said they had felt shock (35%), sadness (31.7%), guilt (23.3%) and discouragement (10%). Anxiety and depression were experienced by 77.5% and 22.5% respectively. In 60% of cases, they stated that the disease was incurable, and the outcome was fatal in 2.5% of cases. The child’s illness was a source of problems in the home in 25% of cases, represented by arguments in 92% and divorce in 8%. In 97.5% of cases, the mother told her family and friends about the child’s illness. In 90% of cases, the mother and child benefited from psychological support from family and friends. Conclusion: Sickle cell disease is a serious illness with a psychological and social impact on mothers. We recommend psychological support for mothers from the moment of diagnosis and throughout follow-up.

The effects of hormone-mediated PI3K/AKT signaling on spermatogenesis in Sertoli cells

The phosphoinositide-3-kinase/Akt(PI3K/AKT)signaling pathway is crucial for Sertoli cell development and completing spermatogenesis.Its main role is to promote proliferation and inhibit apoptosis.Many factors activate the PI3K/AKT pathway,like hormones,such as follicle stimulating hormone(FSH),androgen,estrogen,insulin to name a few.Many of these factors have receptors inside or on the surface of Sertoli cells(SCs).This review summarizes how these hormones directly regulate the PI3K/AKT signaling pathway in SCs,which in turn affects SC proliferation and differentiation.Further,hormone-mediated PI3K/AKT signaling also stimulates SC secretion,which is essential for germ cell development,suggesting an indirect role of PI3K/AKT signaling during spermatogenesis.These functions include promoting spermatogonia proliferation and differentiation,meiosis of spermatocytes,sperm maturation,and their release.This review also provides potential hints for clinically treating male infertility issues like cryptorchidism and Sertoli cell-only syndrome.

Integrin binding peptides facilitate growth and interconnected vascular-like network formation of rat primary cortical vascular endothelial cells in vitro

Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial cells formed interconnected vascular-like network with clearly discernable lumens, which is reminiscent of brain microvascular network in vivo. With the novel integrin-binding array system, we identified the specific types of integrins on brain microvascular endothelial cells that mediate cell adhesion and growth followed by functionalizing a 3 D hydrogel culture system using the binding peptides that specifically bind to the identified integrins, leading to robust growth and lumenized microvascular-like network formation of brain microvascular endothelial cells in 3 D culture. This technology can be used for in vitro and in vivo vascularization of transplants or brain lesions to promote brain tissue regeneration following neurological insults.

Investigations on the Optimization of Contacts Barrier Height for the Improved Performance of ZnO/CdS/CZTS Solar Cells

The numerical simulations were performed using the AMPS-1D simulator to study the effects of the CZTS as an absorber layer and the contacts’barrier height on the performance of four ZnO/CdS/CZTS solar cells.To obtain the best cell performances,the barrier heights of the back and front contacts were adjusted between 0.01,0.77,0.5,and 1.55 eV,respectively.For simulations,we used the lifetime mode,and the device performances were evaluated under AM1.5 illumination spectra.We found that the efficiency,fill factor,and open-circuit voltage were almost constant at a front contact barrier height of less than 0.31 eV.The short-current density was not affected by the front contact barrier height.The back contact material had a significant impact on the CZTS cells parameters.The best performance was obtained for the CZTS550 cell with JSC=29.53 mA/cm2,VOC=1.07 V,FF=0.88,andη=28.08%at barrier heights of 0.31 and 1.55 eV for front and back contacts,respectively.The conduction band offset at the CZTS550/CdS hetero-junction was found to be spike-like with 0.21 eV.The obtained conversion efficiency is comparable to those previously reported in the literature.

Three-dimensional structure of liver vessels and spatial distribution of hepatic immune cells

As the largest internal organ of the human body,the liver has an extremely complex vascularnetwork and multiple types of immune cells.It plays an important role in blood circulation,material metabolism,and immune response.Optical imaging is an effective tool for studying finevascular structure and immunocyte distribution of the liver.Here,we provide an overview of thestructure and composition of liver vessels,the threedimensional(3D)imaging of the liver,andthe spatial distribution and immune function of various cell components of the liver.Especially,we emphasize the 3D imaging methods for visualizing fine structure in the liver.Finally,wesummarize and prospect the development of 3D imaging of liver vesels and immune cells.