Relationship between the components of mare breast milk and foal gut microbiome: shaping gut microbiome development after birth.

The gut microbiota (GM) is essential for mammalian health. Although the association between infant GM and breast milk (BM) composition has been well established in humans, such a relationship has not been investigated in horses. Hence, this study was conducted to analyze the GM formation of foals during lactation and determine the presence of low-molecular-weight metabolites in mares' BM and their role in shaping foals' GM. The fecal and BM samples from six pairs of foals and mares were subjected to 16S ribosomal RNA metagenomic and metabolomic analyses, respectively. The composition of foal GM changed during lactation time; hierarchical cluster analysis divided the fetal GM into three groups corresponding to different time points in foal development. The level of most metabolites in milk decreased over time with increasing milk yield, while threonic acid and ascorbic acid increased. Further analyses revealed gut bacteria that correlated with changes in milk metabolites; for instance, there was a positive correlation between Bacteroidaceae in the foal's gut microbiota and serine/glycine in the mother's milk. These findings help improve the rearing environment of lactating horses and establish artificial feeding methods for foals.

Smart/stimuli-responsive chitosan/gelatin and other polymeric macromolecules natural hydrogels vs. synthetic hydrogels systems for brain tissue engineering: A state-of-the-art review.

Currently, there are no viable curative treatments that can enhance the central nervous system's (CNS) recovery from trauma or illness. Bioengineered injectable smart/stimuli-responsive hydrogels (SSRHs) that mirror the intricacy of the CNS milieu and architecture have been suggested as a way to get around these restrictions in combination with medication and cell therapy. Additionally, the right biophysical and pharmacological stimuli are required to boost meaningful CNS regeneration. Recent research has focused heavily on developing SSRHs as cutting-edge delivery systems that can direct the regeneration of brain tissue. In the present article, we have discussed the pathology of brain injuries, and the applicable strategies employed to regenerate the brain tissues. Moreover, the most promising SSRHs for neural tissue engineering (TE) including alginate (Alg.), hyaluronic acid (HA), chitosan (CH), gelatin, and collagen are used in natural polymer-based hydrogels and thoroughly discussed in this review. The ability of these hydrogels to distribute bioactive substances or cells in response to internal and external stimuli is highlighted with particular attention. In addition, this article provides a summary of the most cutting-edge techniques for CNS recovery employing SSRHs for several neurodegenerative diseases.

Adipose Stem Cell-Seeded Decellularized Porcine Pericardium: A Promising Functional Biomaterial to Synergistically Restore the Cardiac Functions Post-Myocardial Infarction.

Myocardial infarction (MI) is a serious cardiovascular disease as the leading cause of death globally. Hence, reconstruction of the cardiac tissue comes at the forefront of strategies adopted to restore heart functions following MI. In this investigation, we studied the capacity of rat adipose-derived mesenchymal stem cells (r-AdMSCs) and decellularized porcine pericardium (DPP) to restore heart functions in MI animals. MI was induced in four different groups, three of which were treated either using DPP (MI-DPP group), stem cells (MI-SC group), or both (MI-SC/DPP group). Cardiac functions of these groups and the Sham group were evaluated using echocardiography, the intraventricular pressure gradient (IVPG) on weeks 2 and 4, and intraventricular hemodynamics on week 4. On day 31, the animals were euthanized for histological analysis. Echocardiographic, IVPG and hemodynamic findings indicated that the three treatment strategies shared effectively in the regeneration process. However, the MI-SC/DPP group had a unique synergistic ability to restore heart functions superior to the other treatment protocols. Histology showed that the MI-SC/DPP group presented the lowest (p < 0.05) degeneration score and fibrosis % compared to the other groups. Conclusively, stem cell-seeded DPP is a promising platform for the delivery of stem cells and restoration of heart functions post-MI.

Stimuli-responsive hydrogels: smart state of-the-art platforms for cardiac tissue engineering.

Biomedicine and tissue regeneration have made significant advancements recently, positively affecting the whole healthcare spectrum. This opened the way for them to develop their applications for revitalizing damaged tissues. Thus, their functionality will be restored. Cardiac tissue engineering (CTE) using curative procedures that combine biomolecules, biomimetic scaffolds, and cells plays a critical part in this path. Stimuli-responsive hydrogels (SRHs) are excellent three-dimensional (3D) biomaterials for tissue engineering (TE) and various biomedical applications. They can mimic the intrinsic tissues' physicochemical, mechanical, and biological characteristics in a variety of ways. They also provide for 3D setup, adequate aqueous conditions, and the mechanical consistency required for cell development. Furthermore, they function as competent delivery platforms for various biomolecules. Many natural and synthetic polymers were used to fabricate these intelligent platforms with innovative enhanced features and specialized capabilities that are appropriate for CTE applications. In the present review, different strategies employed for CTE were outlined. The light was shed on the limitations of the use of conventional hydrogels in CTE. Moreover, diverse types of SRHs, their characteristics, assembly and exploitation for CTE were discussed. To summarize, recent development in the construction of SRHs increases their potential to operate as intelligent, sophisticated systems in the reconstruction of degenerated cardiac tissues.

Comparison of Bovine- and Porcine-Derived Decellularized Biomaterials: Promising Platforms for Tissue Engineering Applications.

Animal-derived xenogeneic biomaterials utilized in different surgeries are promising for various applications in tissue engineering. However, tissue decellularization is necessary to attain a bioactive extracellular matrix (ECM) that can be safely transplanted. The main objective of the present study is to assess the structural integrity, biocompatibility, and potential use of various acellular biomaterials for tissue engineering applications. Hence, a bovine pericardium (BP), porcine pericardium (PP), and porcine tunica vaginalis (PTV) were decellularized using a Trypsin, Triton X (TX), and sodium dodecyl sulfate (SDS) (Trypsin + TX + SDS) protocol. The results reveal effective elimination of the cellular antigens with preservation of the ECM integrity confirmed via staining and electron microscopy. The elasticity of the decellularized PP (DPP) was markedly (p < 0.0001) increased. The tensile strength of DBP, and DPP was not affected after decellularization. All decellularized tissues were biocompatible with persistent growth of the adipose stem cells over 30 days. The staining confirmed cell adherence either to the peripheries of the materials or within their matrices. Moreover, the in vivo investigation confirmed the biocompatibility and degradability of the decellularized scaffolds. Conclusively, Trypsin + TX + SDS is a successful new protocol for tissue decellularization. Moreover, decellularized pericardia and tunica vaginalis are promising scaffolds for the engineering of different tissues with higher potential for the use of DPP in cardiovascular applications and DBP and DPTV in the reconstruction of higher-stress-bearing abdominal walls.

Impact of Adipose Tissue Depot Harvesting Site on the Multilineage Induction Capacity of Male Rat Adipose-Derived Mesenchymal Stem Cells: An In Vitro Study.

Recently, substantial attention has been paid toward adipose-derived mesenchymal stem cells (AdMSCs) as a potential therapy in tissue engineering and regenerative medicine applications. Rat AdMSCs (r-AdMSCs) are frequently utilized. However, the influence of the adipose depot site on the multilineage differentiation potential of the r-AdMSCs is still ambiguous. Hence, the main objective of this study was to explore the influence of the adipose tissue harvesting location on the ability of r-AdMSCs to express the stem-cell-related markers and pluripotency genes, as well as their differentiation capacity, for the first time. Herein, we have isolated r-AdMSCs from the inguinal, epididymal, peri-renal, and back subcutaneous fats. Cells were compared in terms of their phenotype, immunophenotype, and expression of pluripotency genes using RT-PCR. Additionally, we investigated their potential for multilineage (adipogenic, osteogenic, and chondrogenic) induction using special stains confirmed by the expression of the related genes using RT-qPCR. All cells could positively express stem cell marker CD 90 and CD 105 with no significant in-between differences. However, they did not express the hematopoietic markers as CD 34 and CD 45. All cells could be induced successfully. However, epididymal and inguinal cells presented the highest capacity for adipogenic and osteogenic differentiation (21.36-fold and 11.63-fold for OPN, 29.69-fold and 26.68-fold for BMP2, and 37.67-fold and 22.35-fold for BSP, respectively, in epididymal and inguinal cells (p < 0.0001)). On the contrary, the subcutaneous cells exhibited a superior potential for chondrogenesis over the other sites (8.9-fold for CHM1 and 5.93-fold for ACAN, (p < 0.0001)). In conclusion, the adipose tissue harvesting site could influence the differentiation capacity of the isolated AdMSCs. To enhance the results of their employment in various regenerative cell-based therapies, it is thus vital to take the collection site selection into consideration.

Impact of the mother's gut microbiota on infant microbiome and brain development.

The link between the gut microbiome and health has recently garnered considerable interest in its employment for medicinal purposes. Since the early microbiota exhibits more flexibility compared to that of adults, there is a considerable possibility that altering it will have significant consequences on human development. Like genetics, the human microbiota can be passed from mother to child. This provides information on early microbiota acquisition, future development, and prospective chances for intervention. The succession and acquisition of early-life microbiota, modifications of the maternal microbiota during pregnancy, delivery, and infancy, and new efforts to understand maternal-infant microbiota transmission are discussed in this article. We also examine the shaping of mother-to-infant microbial transmission, and we then explore possible paths for future research to advance our knowledge in this area.

miRNAs insights into rheumatoid arthritis: Favorable and detrimental aspects of key performers.

Rheumatoid arthritis (RA) is a severe autoimmune inflammation that mostly affects the joints. It's a multifactorial disease. Its clinical picture depends on genetic and epigenetic factors such as miRNAs. The miRNAs are small noncoding molecules that are able to negatively or positively modulate their target gene expression. In RA, miRNAs are linked to its pathogenesis. They disrupt immunity balance by controlling granulocytes, triggering the release of several proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, finally leading to synovium hyperplasia and inflammation. Besides, they also may trigger activation of some pathways as nuclear factor kappa-ß disrupts the balance between osteoclast and osteoblast activity, leading to increased bone destruction. Moreover, miRNAs are also applied with efficiency in RA diagnosis and prognosis. Besides the significant association between miRNAs and RA response to treatment, they are also applied as a choice for treatment based on their effects on the immune system and inflammatory cytokines. Hence, the review aims to present an updated overview of miRNAs, their biogenesis, implications in RA pathogenesis, and finally, the role of miRNAs in RA treatment.

Mutations in SARS-CoV-2: Insights on structure, variants, vaccines, and biomedical interventions.

COVID-19 is a worldwide pandemic caused by SARS-coronavirus-2 (SARS-CoV-2). Less than a year after the emergence of the Covid-19 pandemic, many vaccines have arrived on the market with innovative technologies in the field of vaccinology. Based on the use of messenger RNA (mRNA) encoding the Spike SARS-Cov-2 protein or on the use of recombinant adenovirus vectors enabling the gene encoding the Spike protein to be introduced into our cells, these strategies make it possible to envisage the vaccination in a new light with tools that are more scalable than the vaccine strategies used so far. Faced with the appearance of new variants, which will gradually take precedence over the strain at the origin of the pandemic, these new strategies will allow a much faster update of vaccines to fight against these new variants, some of which may escape neutralization by vaccine antibodies. However, only a vaccination policy based on rapid and massive vaccination of the population but requiring a supply of sufficient doses could make it possible to combat the emergence of these variants. Indeed, the greater the number of infected individuals, the faster the virus multiplies, with an increased risk of the emergence of variants in these RNA viruses. This review will discuss SARS-CoV-2 pathophysiology and evolution approaches in altered transmission platforms and emphasize the different mutations and how they influence the virus characteristics. Also, this article summarizes the common vaccines and the implication of the mutations and genetic variety of SARS-CoV-2 on the COVID-19 biomedical arbitrations.

The Pivotal Role of Stem Cells in Veterinary Regenerative Medicine and Tissue Engineering.

The introduction of new regenerative therapeutic modalities in the veterinary practice has recently picked up a lot of interest. Stem cells are undifferentiated cells with a high capacity to self-renew and develop into tissue cells with specific roles. Hence, they are an effective therapeutic option to ameliorate the ability of the body to repair and engineer damaged tissues. Currently, based on their facile isolation and culture procedures and the absence of ethical concerns with their use, mesenchymal stem cells (MSCs) are the most promising stem cell type for therapeutic applications. They are becoming more and more well-known in veterinary medicine because of their exceptional immunomodulatory capabilities. However, their implementation on the clinical scale is still challenging. These limitations to their use in diverse affections in different animals drive the advancement of these therapies. In the present article, we discuss the ability of MSCs as a potent therapeutic modality for the engineering of different animals' tissues including the heart, skin, digestive system (mouth, teeth, gastrointestinal tract, and liver), musculoskeletal system (tendons, ligaments, joints, muscles, and nerves), kidneys, respiratory system, and eyes based on the existing knowledge. Moreover, we highlighted the promises of the implementation of MSCs in clinical use in veterinary practice.

Intraventricular pressure gradient: A novel tool to assess the post-infarction chronic congestive heart failure.

Congestive heart failure (CHF), the leading cause of death, is deemed a grave sequel of myocardial infarction (MI). The employment of left ventricular end-diastolic pressure (LVEDP), as a primary indication of CHF, becomes restricted owing to the potential impairment of heart function and caused injury to the aortic valve during its measurement. Echocardiography is the standard technique to detect cardiac dysfunction. However, it exhibits a low capacity to predict the progression of CHF post chronic MI. Being extremely sensitive, noninvasive, and preload-independent, intraventricular pressure gradient (IVPG) was lately introduced to evaluate cardiac function, specifically during cardiomyopathy. Yet, the utility of its use to assess the CHF progression after chronic MI was not investigated. Herein, in the current research, we aimed to study the efficacy of a novel echocardiographic-derived index as IVPG in the assessment of cardiac function in a chronic MI rat model with CHF. Fifty healthy male rats were involved, and MI was surgically induced in 35 of them. Six months post-surgery, all animals were examined using transthoracic conventional and color M-mode echocardiography (CMME) for IVPG. Animals were euthanized the following day after hemodynamics recording. Gross pathological and histological evaluations were performed. J-tree cluster analysis was conducted relying on ten echocardiographic parameters suggestive of CHF. Animals were merged into two main clusters: CHF+ (MI/HF + group, n = 22) and CHF- (n = 28) that was joined from Sham (n = 15), and MI/HF- (n = 13) groups. MI/HF+ group showed the most severe echocardiographic, hemodynamic, anatomic, and histologic alterations. There was no significant change in the total IVPG among various groups. However, the basal IVPG was significantly increased in MI/HF+ group compared to the other groups. The remaining IVPG measures were considerably increased in the MI/HF+ group than in the Sham one. The segmental IVPG measures were significantly correlated with the anatomical, histological, echocardiographic, and hemodynamic findings except for the heart rate. Moreover, they were significant predictors of CHF following a long-standing MI. Conclusively, IVPG obtained from CMME is a substantially promising noninvasive tool with a high ability to detect and predict the progression of CHF following chronic MI compared to conventional echocardiography.

Smart/stimuli-responsive hydrogels: Cutting-edge platforms for tissue engineering and other biomedical applications.

Recently, biomedicine and tissue regeneration have emerged as great advances that impacted the spectrum of healthcare. This left the door open for further improvement of their applications to revitalize the impaired tissues. Hence, restoring their functions. The implementation of therapeutic protocols that merge biomimetic scaffolds, bioactive molecules, and cells plays a pivotal role in this track. Smart/stimuli-responsive hydrogels are remarkable three-dimensional (3D) bioscaffolds intended for tissue engineering and other biomedical purposes. They can simulate the physicochemical, mechanical, and biological characters of the innate tissues. Also, they provide the aqueous conditions for cell growth, support 3D conformation, provide mechanical stability for the cells, and serve as potent delivery matrices for bioactive molecules. Many natural and artificial polymers were broadly utilized to design these intelligent platforms with novel advanced characteristics and tailored functionalities that fit such applications. In the present review, we highlighted the different types of smart/stimuli-responsive hydrogels with emphasis on their synthesis scheme. Besides, the mechanisms of their responsiveness to different stimuli were elaborated. Their potential for tissue engineering applications was discussed. Furthermore, their exploitation in other biomedical applications as targeted drug delivery, smart biosensors, actuators, 3D and 4D printing, and 3D cell culture were outlined. In addition, we threw light on smart self-healing hydrogels and their applications in biomedicine. Eventually, we presented their future perceptions in biomedical and tissue regeneration applications. Conclusively, current progress in the design of smart/stimuli-responsive hydrogels enhances their prospective to function as intelligent, and sophisticated systems in different biomedical applications.

Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.

Cancer, a major public health problem, is one of the world's top leading causes of death. Common treatments for cancer include cytotoxic chemotherapy, surgery, targeted drugs, endocrine therapy, and immunotherapy. However, despite the outstanding achievements in cancer therapies during the last years, resistance to conventional chemotherapeutic agents and new targeted drugs is still the major challenge. In the present review, we explain the different mechanisms involved in cancer therapy and the detailed outlines of cancer drug resistance regarding multidrug resistance-associated proteins (MRPs) and their role in treatment failures by common chemotherapeutic agents. Further, different modulators of MRPs are presented. Finally, we outlined the models used to analyze MRP transporters and proposed a future impact that may set up a base or pave the way for many researchers to investigate the cancer MRP further.