Host Reaction Research Articles

Influence of glycodelin on the formation of immune response at the level of T-helpers and T-regulatory cells in an <i>in vivo</i> experiment

Objective. To study the influence of glycodelin on T-helpers and Tregs level in the process of forming an immune response to the introduction of allogeneic bone marrow (BM) cells in a dynamic experiment on Wistar rats. Materials and methods. The original experimental model "host versus transplant reaction" on male Wistar rats without preliminary conditioning in recipients was used in the study. Animals were administered recombinant glycodelin against the background of allogeneic intraperitoneal transplantation of BM cells in a dynamic experiment. The level of peripheral T-helpers (CD4+) and Tregs (CD4+CD25+FOXP3+), and the expression of FOXP3 in the spleen and mesenteric lymph nodes were assessed. The material was collected on the 3rd and 21st days of the experiment. Results. Glycodelin was shown to reduce the absolute number of T-helpers in the peripheral blood (on the 3rd and 21st days) and to increase the proportion of Tregs on the 21st day of the experiment against the background of the introduction of allogeneic BM cells. It was found out, that glycodelin reduced the level of Tregs in the white pulp of the spleen on the 3rd day of the experiment, while the number of these cells on the 21st day increased, reducing the number of T-helpers at the same time. At the level of the mesenteric lymph nodes, glycodelin reduced the level of T-helpers on the 21st day of the experiment, simultaneously increasing the number of Tregs. In general, a unidirectional and distributed effect of glycodelin on the immune response at the level of T-helpers was observed, that was a decrease of T-helpers, but an increase of Tregs on the 21st day of the experiment. Conclusion. Thus, glycodelin had an immunomodulatory effect on T-helpers and Tregs formation. The vector of the obtained effects was immunosuppressive in nature and contributed to the suppression of the immune response to allogeneic cells.

Optimizing CAR-NK Cell Transduction and Expansion: Leveraging Cytokine Modulation for Enhanced Performance.

Cellular immunotherapy has emerged as one of the most potent approaches to treating cancer patients. Adoptive transfer of chimeric antigen receptor (CAR) T cells as well as the use of haploidentical natural killer (NK) cells can induce remission in patients with lymphoma and leukemia. Although the use of CAR T cells has been established, this approach is currently limited for wider use by the risk of severe adverse events, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Moreover, the risk of triggering graft vs host reactions in settings of allogeneic T cell infusion limits the use to autologous CAR T cells if advanced CRISPR engineering is not applied. In contrast, NK cell-based cancer immunotherapy has emerged as a safe approach even in allogeneic settings. However, efficient transduction of primary blood NK cells with vesicular stomatitis virus G glycoprotein (VSV-G) pseudotyped lentivirus commonly used for T cell modification remains challenging. This article presents a detailed method that significantly enhances the transduction efficiency of NK cells by utilizing a short-term culture in cytokine-supplemented medium. It also encompasses the preparation of high-titer and high-quality lentiviral particles for optimal NK cell transduction. Overall, this protocol details the step-by-step culture of NK cells in cytokine-supplemented medium, their transduction with VSV-G lentiviral vectors, and subsequent expansion for functional assays. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Isolation of NK cells from human peripheral blood mononuclear cells (PBMCs) Basic Protocol 2: NK cell expansion and transduction with lentivirus for generating CAR-NK cells Support Protocol 1: Plasmid amplification Support Protocol 2: Lentivirus preparation Support Protocol 3: Lentivirus titration.

The mechanisms of Zika virus-induced neuropathogenesis.

Zika virus (ZIKV), a flavivirus, is one of the most serious re-emerging pathogens. Growing outbreaks in the Americas have linked ZIKV to significant clinical symptoms including Guillain-Barré syndrome in adults and congenital anomalies in newborns. ZIKV affects brain cells in a variety of ways, mostly apoptosis and cell cycle delays. Modulation of the host's immune reaction and the inflammatory process has also been shown to be involved in ZIKV-induced neurological disorders. This review summarized and discussed the latest advances in ZIKV research to shed fresh light on the multiple mechanisms incolved in ZIKV-induced neuropathogenesis.

Tissue engineering of Cornea via Type 1 Collagen Biomaterials – A perspective

Engineering corneal tissue has advanced significantly in recent years. Engineering a biocompatible, mechanically stable, and optically clear tissue presents significant engineering hurdles. Two fundamental strategies have been explored by scholars to address these issues: cell-based methods for controlling cells their own extracellular matrix and scaffold-based methods for supplying dense, transparent matrices for cell growth. Both approaches have had some level of success. Additionally, new developments in innervating a tissue-engineered construct have been developed. Future research must concentrate on enhancing the mechanical stability of engineered constructions and the host reaction to implantation. Type 1 Collagen Biomaterial has been used for the construction of scaffolds or implantation for the cornea repair. Various methods for fabrication of the scaffolds have been described and mentioned tissue engineering application for cornea repair and regeneration. Given this correspondence, the type 1 collagen was a potential biomaterial for tissue engineering scaffold fabrication for effective regeneration of cornea.

Tuning interfacial molecular asymmetry to engineer protective coatings with superior surface anchoring, antifouling and antibacterial properties

Multifunctional robust protective coatings that combine biocompatibility, antifouling and antimicrobial properties play an essential role in reducing host reactions and infection on invasive medical devices. However, developing these protective coatings generally faces a paradox: coating materials capable of achieving robust adhesion to substrates via spontaneous deposition inevitably initiate continuous biofoulant adsorption, while those employing strong hydration capability to resist biofoulant attachment have limited substrate binding ability and durability under wear. Herein, we designed a multifunctional terpolymer of poly(dopamine methyacrylamide-co-2-methacryloyloxyethyl phoasphorylcholine-co-2-(dimethylamino)-ethyl methacrylate) (P(DMA-co-MPC-co-DMAEMA)), which integrates desired yet traditionally incompatible functions (i.e., robust adhesion, antifouling, lubrication, and antimicrobial properties). Direct normal and lateral force measurements, dynamic adsorption tests, surface ion conductance mapping were applied to comprehensively investigate the nanomechanics of coating-biofloulant interactions. Catechol groups of DMA act as basal anchors for robust substrate deposition, while the highly hydrated zwitterion of MPC provides apical protection to resist biofouling and wear. Moreover, the antimicrobial property is conferred through the protonation of tertiary amine groups on DMAEMA, inhibiting infection under physiological conditions. This work provides an effective strategy for harmonizing demanded yet incompatible properties in one coating material, with significant implications for the development of multifunctional surfaces towards the advancement of invasive biomedical devices. Statement of significanceMultifunctional robust protective coatings have been widely utilized in invasive medical devices to mitigate host responses and infection. However, modified surface coatings often encounter a trade-off between robust adhesion to substrates and strong hydration capability for antifouling and antimicrobial properties. We propose a universal strategy for surface modification by dopamine-assisted co-deposition with a multifunctional terpolymer of P(DMA-co-MPC-co-DMAEMA) that simultaneously achieves robust adhesion, antifouling, and antimicrobial properties. Through elucidating the nanomechanics with fundamentally understanding the interactions between the coating and biomacromolecules, we highlight the role of DMA for substrate adhesion, MPC for biofouling resistance, and DMAEMA for antimicrobial activity. This approach presents a promising strategy for constructing multifunctional coatings on minimally invasive medical devices by tuning interfacial molecular asymmetricity to reconcile incompatible properties within one coating.

Evaluation of biocompatibility and osseointegration of multi-component TiAl6V4 titanium alloy implants.

This study aimed to investigate the biocompatibility and osseointegration of novel titanium (Ti) implants with a perforated part with high surface roughness (Ra >4 μm) and a smooth solid part (test group), as compared to smooth solid Ti implants (control group; Ra < 0.8 μm). Test and control implants were implanted in rabbit femurs. After 4 and 15 weeks, host tissue reaction and quality of tissue formed were evaluated with histopathology, while micro-CT scans were used to quantitatively assess bone-implant contact (BIC), surrounding bone formation, and bone ingrowth. After 4 and 15 weeks, minimal host reaction was found in the test group. Histopathological analysis showed new bone formation around the implants in both the test and control groups after 4 weeks. Furthermore, additional bone growth was often observed within the holes of the test implants. After 15 weeks, the test implants showed high bone ingrowth and the presence of mature bone in direct contact with the implant surface, whereas, bone ingrowth was poorer for the control group with 30% of the control implants, showing larger gaps at the bone-implant interface. Quantitative micro-CT analysis revealed comparable BIC and bone formation in both groups at 4 weeks, but higher BIC and more bone formation in the test group than in the control group after 15 weeks. No significant differences were observed in any of the analyses. In conclusion, partially perforated, high-roughness Ti implants showed excellent osseointegration and minimal host reaction, indicating their potential for orthopedic applications in bone repair and regeneration.

594. THE IMPACT OF PATIENT CHARACTERISTICS AND NEOADJUVANT TREATMENT ON THE TUMOUR MICRO-ENVIRONMENT OF ESOPHAGEAL CANCER

Abstract Background Esophageal cancer remains associated with poor prognosis, as even with the current standards of multimodal treatment and oncologic surgery many patients show no response to treatment, or suffer early recurrence after surgery. In the current era of precision medicine, a better understanding of the tumor microenvironment (TME) is needed to identify patients with unfavourable biology, but also to illustrate the physiopathology of host reaction to treatment. The aim of this monocentric translational study was to analyse the biomolecular characteristics of esophageal cancer in relation to key clinicopathologic parameters, and in particular to the response to neoadjuvant treatment. Methods A series of patients operated for esophageal cancer with curative intent between 01.2009 and 12.2021 were included in this study. Clinicopathological data were collected, and initial biopsies and surgical specimens were reassessed by a senior GI pathologist. The immune infiltrate markers CD3, CD8, CD163, CD68, PDL1and FOXP3 were recorded as cell counts/high power field. The CPS score was used for PD-L1 quantification, whereas the Mandard regression grade (TRG) assessed pathologic response to neoadjuvant treatment (NAT). Continuous variables were compared with the Mann-Whitney-U and ANOVA tests, and categorical ones with the Chi-2 test. Significance threshold was set at p&amp;lt;0.05. Results Overall, 68 patients (82.4% males, mean age 62.4□9.4 years, 79.4% adenocarcinoma) were included. TME in smokers had lower M2-like (CD163+, p=0.009) and total macrophages (CD68+, p=0.001), but similar CD163/68 ratio and T-cells as non-smokers. Adenocarcinoma histology compared to squamous cell, showed higher M2-like macrophages (p=0.023), mean CPS score (p=0.038) and T-cell infiltration (p=0.006). NAT increased macrophages and cytotoxic T-cells, and decreased Treg/FoxP3 cells in the TME. Chemotherapy, compared to chemoradiation, was associated with higher T-cell TME infiltration. Good responders to NAT (TRG1-2) had similar initial TME characteristics as poor responders, but they displayed lower macrophage count upon final histology (p=0.003). Conclusions In the present series, active smoking was related to attenuated, whereas adenocarcinoma histology to enhanced M2-like macrophage infiltration of esophageal cancer TME. Neoadjuvant treatment, and especially chemotherapy, recruited macrophages and T-cells in the TME. None of the biomarkers derived from the initial biopsies were associated with response to NAT, although an increased macrophage count upon final histology was related to poor response. The present study provides valuable insight to the TME composition of esophageal cancer. However, further studies are needed to assess the exact functional role of TME elements, and specifically macrophages, and their impact on clinical outcomes.

From immune dysregulation to organ dysfunction: understanding the enigma of Sepsis.

Sepsis is a syndrome precipitated by immune dysregulation in response to infection, and represents a pivotal factor in global mortality attributed to diseases. The recent consensus delineates sepsis as a perilous state of organ dysfunction arising from the host's maladaptive reaction to infection. It masks the complexity and breadth of the immune mechanisms involved in sepsis, which is characterized by simultaneous hyperinflammation and immunosuppression. Sepsis is highly correlated with the dysregulation of immune response, which is mainly mediated by various immune cells and their interactions. This syndrome can lead to a plethora of complications, encompassing systemic inflammatory response, metabolic disturbances, infectious shock, MODS, and DIC. Furthermore, more research studies have been conducted on sepsis in the past few years. The pathological characteristics of sepsis have been improved or treated by targeting signaling pathways like NF-B, JAK-STAT, PI3K-Akt, and p38-MAPK. Combined drug therapy is better than single drug therapy for sepsis. This article will review the latest progress in the pathogenesis and treatment of sepsis.

Types of cell death and their relations to host immunological pathways.

Various immune pathways have been identified in the host, including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. While TH2 and TH9 responses primarily target multicellular parasites, host immune pathways directed against viruses, intracellular microorganisms (such as bacteria, protozoa, and fungi), and extracellular microorganisms can employ programmed cell death mechanisms to initiate immune responses or execute effective strategies for pathogen elimination. The types of programmed cell death involved include apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, and NETosis. Specifically, apoptosis is associated with host anti-virus eradicable THαβ immunity, autophagy with host anti-virus tolerable TH3 immunity, pyroptosis with host anti-intracellular microorganism eradicable TH1 immunity, ferroptosis with host anti-intracellular microorganism tolerable TH1-like immunity, necroptosis with host anti-extracellular microorganism eradicable TH22 immunity, and NETosis with host anti-extracellular microorganism tolerable TH17 immunity.

HLA Awareness in tissue decellularization: A paradigm shift for enhanced biocompatibility, studied on the model of the human fascia lata graft

Last twenties, tissue engineering has rapidly advanced to address the shortage of organ donors. Decellularization techniques have been developed to mitigate immune rejection and alloresponse in transplantation. However, a clear definition of effective decellularization remains elusive. This study compares various decellularization protocols using the human fascia lata model. Morphological, structural and cytotoxicity/viability analyses indicated that all the five tested protocols were equivalent and met Crapo's criteria for successful decellularization. Interestingly, only the in vivo immunization test on rats revealed differences. Only one protocol exhibited Human Leucocyte Antigen (HLA) content below 1% residual threshold, the only criterion preventing rat immunization with an absence of rat anti-human IgG switch after one month (N=4 donors for each of the 7 groups, added by negative and positive controls, n=28). By respecting a refined set of criteria, i.e. lack of visible nuclear material, <50ng DNA/mg dry weight of extracellular matrix, and <1% residual HLA content, the potential for adverse host reactions can be drastically reduced. In conclusion, this study emphasizes the importance of considering not only nuclear components but also major histocompatibility complex in decellularization protocols and proposes new guidelines to promote safer clinical development and use of bioengineered scaffolds.

Human gut microbiota-reactive DP8α Tregs prevent acute graft-versus-host disease in a CD73-dependent manner.

Graft-versus-host disease (GvHD) is a life-threatening complication frequently occurring following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since gut microbiota and regulatory T cells (Tregs) are believed to play roles in GvHD prevention, we investigated whether DP8α Tregs, which we have previously described to harbor a T cell receptor specificity for the gut commensal Faecalibacterium prausnitzii, could protect against GvHD, thereby linking the microbiota and its effect on GvHD. We observed a decrease in CD73+ DP8α Treg frequency in allo-HSCT patients 1 month after transplantation, which was associated with acute GvHD (aGvHD) development at 1 month after transplantation, as compared with aGvHD-free patients, without being correlated to hematological disease relapse. Importantly, CD73 activity was shown to be critical for DP8α Treg suppressive function. Moreover, the frequency of host-reactive DP8α Tregs was also lower in aGvHD patients, as compared with aGvHD-free patients, which could embody a protective mechanism responsible for the maintenance of this cell subset in GvHD-free patients. We also showed that human DP8α Tregs protected mice against xenogeneic GvHD through limiting deleterious inflammation and preserving gut integrity. Altogether, these results demonstrated that human DP8α Tregs mediate aGvHD prevention in a CD73-dependent manner, likely through host reactivity, advocating for the use of these cells for the development of innovative therapeutic strategies to preclude aGvHD-related inflammation.

A Comprehensive Review Exploring the Protective Role of Specific Commensal Gut Bacteria against Salmonella.

Gut microbiota is a diverse community of microorganisms that constantly work to protect the gut against pathogens. Salmonella stands out as a notorious foodborne pathogen that interacts with gut microbes, causing an imbalance in the overall composition of microbiota and leading to dysbiosis. This review focuses on the interactions between Salmonella and the key commensal bacteria such as E. coli, Lactobacillus, Clostridium, Akkermansia, and Bacteroides. The review highlights the role of these gut bacteria and their synergy in combating Salmonella through several mechanistic interactions. These include the production of siderophores, which compete with Salmonella for essential iron; the synthesis of short-chain fatty acids (SCFAs), which exert antimicrobial effects and modulate the gut environment; the secretion of bacteriocins, which directly inhibit Salmonella growth; and the modulation of cytokine responses, which influences the host's immune reaction to infection. While much research has explored Salmonella, this review aims to better understand how specific gut bacteria engage with the pathogen, revealing distinct defense mechanisms tailored to each species and how their synergy may lead to enhanced protection against Salmonella. Furthermore, the combination of these commensal bacteria could offer promising avenues for bacteria-mediated therapy during Salmonella-induced gut infections in the future.

Application of advanced bioimaging technologies in viral infections

Viruses are major pathogens responsible for a wide range of infectious diseases that may lead to global pandemics. The understanding of structural underpinnings of virions, molecular mechanisms of infection and the pathogenesis of viral diseases is crucial for exploring prophylactic and therapeutic approaches for viral disorders. Though the latest developments in imaging techniques have equipped scientists with tools to investigate viral infections in unprecedented detail with multiple spatial and temporal resolutions, the unveiling of how viral particles dynamically interact with host cells requires integrations of strategies connecting the structural complexity with functional properties. Here, we aim to delineate (1) the diversity of imaging devices that have been applied in the investigation of viral morphology and structure, (2) the contribution of current imaging techniques in revealing features of viral life-cycle and the associated host reactions, and (3) the potential of imaging systems in the diagnosis and prognosis of viral diseases. This review provides an essential overview of bioimaging techniques in scenarios of viral infections and comes up with instructions of how to select appropriate bioimaging methods for virological studies based on specific objectives of investigations. Additionally, we discuss the challenges and opportunities of microscopy imaging in promoting more insightful comprehension of complexities between viruses and hosts in the nano-scale range.

Aphelenchoides besseyi Parasitizing Tobacco Cultivars in Brazil.

Foliar nematodes (Aphelenchoides spp.) are known to be parasites of tobacco in restricted areas, but symptoms caused by A. besseyi in tobacco are not well characterized, despite the great importance of this nematode worldwide. This study aimed to evaluate the host reaction of four Nicotiana tabacum cultivars (Comum, Xanthi, Samsun, and TNN) and N. benthamiana cultivar Comum to A. besseyi and to characterize the symptoms and the parasitism of this nematode. Two experiments were conducted under greenhouse conditions with controlled humidity and temperature, in which the plants were inoculated with 600 A. besseyi. At 30 days after inoculation (DAI), nematodes present in the soil, roots, and shoot parts were extracted, and roots and shoot tissues were stained with acid fuchsin. A high number of A. besseyi was obtained per gram of shoot tissues (125 to 2,169 nematodes), and severe symptoms were observed in leaves and inflorescences of all cultivars. The symptoms included foliar distortion and deformation, necrotic spots delimited by the veins, flower abortion, and poor development of plants. In addition, A. besseyi was observed to penetrate tobacco roots at 30 DAI, and nematodes were also observed in the foliar mesophyll, inflorescences, and stems, a parasitism that has not been previously reported in tobacco plants. The disease caused by A. besseyi in tobacco could be a concern for growers in southern and northeastern Brazil because this nematode can cause severe damage to the marketable leaves of tobacco, reducing its commercial value.

The Hidden World Within: Microbial Dynamics in Root Canal Systems.

Several hundred different microbial taxa have made the oral cavity their home because of their evolution in multiple species communities within the special ecosystem. On the other hand, the dental pulpor internal tissue of the tooth is a connective tissue that is physiologically sterile and where any microbial infiltration is a harmfulindication. It causes the pulp tissue to become inflamed, which leads to the death of the pulp and diffuses infection with inflammation to the peri-radicular tissues. Comprehending the biology of biofilms, the microbial makeup, and the host's reaction to infections in the pathobiology of root canal infectionshas received a lot of attention throughout the last few decades. Such comprehensive knowledge is required to design preventive medicines as well as clinically effective treatment regimens. Surprisingly, clinical approaches have concentrated more on radiographically perfecting channel preparation than on debridement of these intricate root canal systems, despite the clear realization that root canal infections are biofilm mediated. Since the present comprehension of the microbial etiopathogenesis of apical periodontitis highlights the significance of focusing on procedures such as "canal cleaning" and chemo-mechanical disinfection, the exclusive purpose of endodontic therapy is mainly missed while discussing "canal shaping."We thoroughly examine the state of our knowledge of the composition and functional traits of the root canal microbiome in this review. We also go into the difficulties with root canal disinfection and the cutting-edge approaches that try to solve these difficulties. In conclusion, we present essential guidance for prospective research areas, underscoring their significance as crucial considerations in the field of frontiers in oral health.

The Host Range of Fusarium proliferatum in Western Canada.

Fusarium proliferatum is associated with the root rot of many plant species, but knowledge of its impact on western Canadian field crops is limited. This study assessed the host range of this fungus and its effect on plant emergence, plant height, and shoot and root dry weights in repeated greenhouse experiments with wheat, barley, faba beans, peas, lentils, canola, lupine, and soybeans. Infection was confirmed via PCR, and principal component analysis determined the utility of different parameters in assessing host responses. All crops were at least partly susceptible, developing mild to severe disease at the seedling and adult stages, and showing significant reductions in growth. In general, the barley and wheat demonstrated higher tolerances to infection, followed by the faba bean and the pea. The soybean, canola, lupine, and lentil were most susceptible. The canola and the soybean were particularly vulnerable to F. proliferatum at the pre-emergence stage, while infection greatly reduced the lentil's biomass. Reductions in the barley's emergence and other growth parameters, however, occurred only under a high inoculum concentration. Variability in root rot severity among cultivars of the same crop indicated some diversity in host reactions within species. Nonetheless, the absence of fully-resistant crops may pose challenges in managing F. proliferatum in western Canadian cropping systems.

Molecular characterization and host reaction to tomato mottle mosaic virus isolated from sweet pepper seeds in Japan.

Many countries have identified tomato mottle mosaic virus (ToMMV) as a serious threat to tomato production. Here, we constructed and characterized infectious clones of ToMMV isolated from Japanese sweet pepper seeds. The genome of the Japanese isolate is 6399 nucleotides in length and exhibits thehighest identity withpreviously characterized isolates. For example, it is 99.7% identical to that of the Mauritius isolate, which occurs worldwide. Phylogenetic analysis based on complete genome sequences revealed that the Japanese isolates clustered in the same clade as those from other countries. When homozygous tomato cultivars with tobamovirus resistance genes were inoculated with an infectious cDNA clone of ToMMV, the virus systemically infected tomato plants with symptoms typical of Tm-1-carrying tomato cultivars. In contrast, tomato cultivars carrying Tm-2 or Tm-22 showed symptoms only on the inoculated leaves. Furthermore, when commercial cultivars of Tm-22 heterozygous tomato were inoculated with ToMMV, systemic infections were observed in all cultivars, with infection frequencies ranging from 25 to 100%. Inoculation of heterozygous sweet pepper cultivars with tobamovirus resistance genes (L1, L3, and L4) with ToMMV resulted in an infection frequency of about 70%, but most of the infected L1, L3, and L4 cultivars were symptomless, and 10-20% showed symptoms of necrosis and yellowing. Tomato mosaic virus strain L11A, an attenuated virus, did not provide cross-protection against ToMMV and led to systemic infection with typical symptoms. These results suggest that ToMMV might cause extensive damage to existing tomato and sweet pepper cultivars commonly grown in Japan.

Study on the mechanism of magnesium calcium alloys/mineralized collagen composites mediating macrophage polarization to promote bone repair

Magnesium-based composites are a focal point in biomaterials research. However, the rapid degradation rate of magnesium alloys does not align with the healing time of bone tissue. Additionally, the host reaction caused by magnesium implantation hampers its full osteogenic potential. To maintain an appropriate microenvironment, it is important to enhance both corrosion resistance and osteogenic activity of the magnesium matrix. In this study, a composite scaffold composed of mineralized collagen and magnesium alloy was utilized to investigate the regulatory effect of mineralized collagen on mouse macrophages and evaluate its impact on mouse bone marrow mesenchymal stem cells in terms of osteogenesis, immune response, and macrophage-induced osteogenic differentiation. This experiment examined the biocompatibility of mouse bone marrow mesenchymal stem cells and macrophage-induced osteogenic differentiation in vitro, and examined the expression levels of relevant pathways proteins. Magnesium calcium alloys/mineralized collagen exhibited extensive spreading, facilitated by broad and abundant pseudopodia that firmly adhered them to the material surface and promoted growth and pseudopodia formation. The findings revealed that magnesium calcium alloy/mineralized collagen scaffold materials induced osteogenic differentiation mainly through M2 polarization of macrophages. This effect was mainly mediated by promoting the integrin α2β1-FAK-ERK1/2 signaling pathways and inhibiting the RANK signaling pathways.

Immunological and molecular diagnostic techniques in fish health: present and future prospectus.

Fish health management is critical to aquaculture and fisheries as it directly affects sustainability and productivity. Fish disease diagnosis has taken a massive stride because of advances in immunological and molecular diagnostic tools which provide a sensitive, quick, and accurate means of identifying diseases. This review presents an overview of the main molecular and immunological diagnostic methods for determining the health of fish. The immunological techniques help to diagnose different fish diseases by detecting specific antigens and antibodies. The application of immunological techniques to vaccine development is also examined in this review. The genetic identification of pathogens is made possible by molecular diagnostic techniques that enable the precise identification of bacterial, viral, and parasitic organisms in addition to evaluating host reactions and genetic variation associated with resistance to disease. The combination of molecular and immunological methods has resulted in the creation of novel techniques for thorough evaluation of fish health. These developments improve treatment measures, pathogen identification and provide new information about the variables affecting fish health, such as genetic predispositions and environmental stresses. In the framework of sustainable fish farming and fisheries management, this paper focuses on the importance of these diagnostic techniques that play a crucial role in protecting fish populations and the aquatic habitats. This review also examines the present and potential future directions in immunological and molecular diagnostic techniques in fish health.

Decellularized kidney extracellular matrix-based hydrogels for renal tissue engineering

Kidney regeneration is hindered by the limited pool of intrinsic reparative cells. Advanced therapies targeting renal regeneration have the potential to alleviate the clinical and financial burdens associated with kidney disease. Delivery systems for cells, extracellular vesicles, or growth factors aimed at enhancing regeneration can benefit from vehicles enabling targeted delivery and controlled release. Hydrogels, optimized to carry biological cargo while promoting regeneration, have emerged as promising candidates for this purpose. This study aims to develop a hydrogel from decellularized kidney extracellular matrix (DKECM) and explore its biocompatibility as a biomaterial for renal regeneration. The resulting hydrogel crosslinks with temperature and exhibits a high concentration of extracellular matrix. The decellularization process efficiently removes detergent residues, yielding a pathogen-free biomaterial that is non-hemolytic and devoid of α-gal epitope. Upon interaction with macrophages, the hydrogel induces differentiation into both pro-inflammatory and anti-inflammatory phenotypes, suggesting an adequate balance to promote biomaterial functionality in vivo. Renal progenitor cells encapsulated in the DKECM hydrogel demonstrate higher viability and proliferation than in commercial collagen-I hydrogels, while also expressing tubular cells and podocyte markers in long-term culture.Overall, the injectable biomaterial derived from porcine DKECM is anticipated to elicit minimal host reaction while fostering progenitor cell bioactivity, offering a potential avenue for enhancing renal regeneration in clinical settings. Statement of significanceThe quest to improve treatments for kidney disease is crucial, given the challenges faced by patients on dialysis or waiting for transplants. Exciting new therapies combining biomaterials with cells can revolutionize kidney repair. In this study, researchers created a hydrogel from pig kidney. This gel could be used to deliver cells and other substances that help in kidney regeneration. Despite coming from pigs, it's safe for use in humans, with no harmful substances and reduced risk of immune reactions. Importantly, it promotes a balanced healing response in the body. This research not only advances our knowledge of kidney repair but also offers hope for more effective treatments for kidney diseases.