The fate of adipose tissue and adipose-derived stem cells in allograft.

Utilizing adipose tissue and adipose-derived stem cells (ADSCs) turned into a promising field of allograft in recent years. The therapeutic potential of adipose tissue and ADSCs is governed by their molecular secretions, ability to sustain multi-differentiation and self-renewal which are pivotal in reconstructive, genetic diseases, and cosmetic goals. However, revisiting the existing functional capacity of adipose tissue and ADSCs and their intricate relationship with allograft is crucial to figure out the remarkable question of safety to use in allograft due to the growing evidence of interactions between tumor microenvironment and ADSCs. For instance, the molecular secretions of adipose tissue and ADSCs induce angiogenesis, create growth factors, and control the inflammatory response; it has now been well determined. Though the existing preclinical allograft studies gave positive feedback, ADSCs and adipose tissue are attracted by some factors of tumor stroma. Moreover, allorecognition is pivotal to allograft rejection which is carried out by costimulation in a complement-dependent way and leads to the destruction of the donor cells. However, extensive preclinical trials of adipose tissue and ADSCs in allograft at molecular level are still limited. Hence, comprehensive immunomodulatory analysis could ensure the successful allograft of adipose tissue and ADSCs avoiding the oncological risk.

Comprehensive literature review of monkeypox.

The current outbreak of monkeypox (MPX) infection has emerged as a global matter of concern in the last few months. MPX is a zoonosis caused by the MPX virus (MPXV), which is one of the Orthopoxvirus species. Thus, it is similar to smallpox caused by the variola virus, and smallpox vaccines and drugs have been shown to be protective against MPX. Although MPX is not a new disease and is rarely fatal, the current multi-country MPX outbreak is unusual because it is occurring in countries that are not endemic for MPXV. In this work, we reviewed the extensive literature available on MPXV to summarize the available data on the major biological, clinical and epidemiological aspects of the virus and the important scientific findings. This review may be helpful in raising awareness of MPXV transmission, symptoms and signs, prevention and protective measures. It may also be of interest as a basis for performance of studies to further understand MPXV, with the goal of combating the current outbreak and boosting healthcare services and hygiene practices.Trial registration: ClinicalTrials.gov identifier: NCT02977715..Trial registration: ClinicalTrials.gov identifier: NCT03745131..Trial registration: ClinicalTrials.gov identifier: NCT00728689..Trial registration: ClinicalTrials.gov identifier: NCT02080767..

Nanoparticles for the treatment of glaucoma-associated neuroinflammation.

Recently, a considerable amount of literature has emerged around the theme of neuroinflammation linked to neurodegeneration. Glaucoma is a neurodegenerative disease characterized by visual impairment. Understanding the complex neuroinflammatory processes underlying retinal ganglion cell loss has the potential to improve conventional therapeutic approaches in glaucoma. Due to the presence of multiple barriers that a systemically administered drug has to cross to reach the intraocular space, ocular drug delivery has always been a challenge. Nowadays, studies are focused on improving the current therapies for glaucoma by utilizing nanoparticles as the modes of drug transport across the ocular anatomical and physiological barriers. This review offers some important insights on the therapeutic advancements made in this direction, focusing on the use of nanoparticles loaded with anti-inflammatory and neuroprotective agents in the treatment of glaucoma. The prospect of these novel therapies is discussed in relation to the current therapies to alleviate inflammation in glaucoma, which are being reviewed as well, along with the detailed molecular and cellular mechanisms governing the onset and the progression of the disease.

Targeting Differential Roles of Tumor Necrosis Factor Receptors as a Therapeutic Strategy for Glaucoma.

Glaucoma is an irreversible sight-threatening disorder primarily due to elevated intraocular pressure (IOP), leading to retinal ganglion cell (RGC) death by apoptosis with subsequent loss of optic nerve fibers. A considerable amount of empirical evidence has shown the significant association between tumor necrosis factor cytokine (TNF; TNFα) and glaucoma; however, the exact role of TNF in glaucoma progression remains unclear. Total inhibition of TNF against its receptors can cause side effects, although this is not the case when using selective inhibitors. In addition, TNF exerts its antithetic roles via stimulation of two receptors, TNF receptor I (TNFR1) and TNF receptor II (TNFR2). The pro-inflammatory responses and proapoptotic signaling pathways predominantly mediated through TNFR1, while neuroprotective and anti-apoptotic signals induced by TNFR2. In this review, we attempt to discuss the involvement of TNF receptors (TNFRs) and their signaling pathway in ocular tissues with focus on RGC and glial cells in glaucoma. This review also outlines the potential application TNFRs agonist and/or antagonists as neuroprotective strategy from a therapeutic standpoint. Taken together, a better understanding of the function of TNFRs may lead to the development of a treatment for glaucoma.

Application of liposomes in the treatment of infectious diseases.

The advances in the development of drugs and vaccines for major infectious diseases of tuberculosis (TB), malaria and HIV represent some of the most significant milestones in their therapeutic strategies. Yet, current drugs and vaccines display limitations such as drug resistance and low efficacy level. In recent years, new emerging and advanced nano-technology carrier liposomes have been widely studied towards producing drugs and vaccines capable of targeting infectious diseases. Liposomes portrayed biocompatible and biodegradable properties with versatile flexibility, characteristics that are advantageous for a good targeting at the site of action. The success of liposomes has renewed interest in the research and development of liposomal drugs and vaccines shifting the paradigm in infectious diseases treatment. This review focuses on the limitations of current therapeutic drugs and vaccines, the knowledge of liposomes in terms of their classifications and advantages, and a review of the application of liposomes in the treatment of TB, malaria, and HIV infection.

Adipose-Derived Stem Cell: "Treat or Trick".

Stem cells have been widely used for treating disease due to the various benefits they offer in the curing process. Several treatments using stem cells have undergone clinical trials, such as cell-based therapies for heart disease, sickle cell disease, thalassemia, etc. Adipose-derived stem cells are some of the many mesenchymal stem cells that exist in our body that can be harvested from the abdomen, thighs, etc. Adipose tissue is easy to harvest, and its stem cells can be obtained in higher volumes compared to stem cells harvested from bone marrow, for which a more invasive technique is required with a smaller volume obtained. Many scientists have expressed interest in investigating the role of adipose-derived stem cells in treating disease since their use was first described. This is due to these stem cells' ability to differentiate into multiple lineages and secrete a variety of growth factors and proteins. Previous studies have found that the hormones, cytokines, and growth factors contained in adipose tissue play major roles in the metabolic regulation of adipose tissue, as well as in energy balance and whole-body homeostasis through their endocrine, autocrine, and paracrine functions. These are thought to be important contributors to the process of tissue repair and regeneration. However, it remains unclear how effective and safe ADSCs are in treating diseases. The research that has been carried out to date is in order to investigate the impact of ADSCs in disease treatment, as described in this review, to highlight its "trick or treat" effect in medical treatment.

Liposomes derived from Mycobacterium smegmatis promote immune activation of mice bone marrow-derived dendritic cells.

Background: Tuberculosis (TB) is the leading cause of mortality due to infectious diseases. The development of new generation vaccines against TB is of paramount importance for the control of the disease. In previous studies, liposomes obtained from lipids of Mycobacterium smegmatis (LMs) demonstrated their immunogenicity and protective capacity against Mycobacterium tuberculosis in mice. To characterize the immunomodulatory capacity of this experimental vaccine candidate, in the current study, the stimulatory capacity of LMs was determined on bone marrow-derived dendritic cells (BMDCs) from mice. Methods: LMs were obtained and incubated with mature BMDCs. The internalization of LMs by BMDCs was studied by confocal microscopy, and the LMs immune-stimulatory capacity was determined by the expression of surface molecules (CD86 and MHCII) and the cytokine production (interleukin [IL]-12, interferon-Υ, tumor necrosis factor-α, and IL-10) 24 h after exposure to LMs. Results: The interaction of LMs with BMDCs and its internalization was demonstrated as well as the immune activation of BMDCs, characterized by the increased expression of CD86 and the production of IL-12. The LMs internalization and immune activation of BMDCs were blocked in the presence of cytochalasin, filipin III and chlorpromazine, which demonstrated that internalization of LMs by BMDCs is a key process for the LMs induced immune activation of BMDCs. Conclusions: The results obtained support the further evaluation of LMs as a mycobacterial vaccine, adjuvant, and in immunotherapy.

Mycobacterium smegmatis proteoliposome induce protection in a murine progressive pulmonary tuberculosis model.

Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB vaccine, BCG, is not fully protective against the adult form of the disease and is unable to prevent its transmission although it is still useful against severe childhood TB. Hence, the search for new vaccines is of great interest. In a previous study, we have shown that proteoliposomes obtained from Mycobacterium smegmatis (PLMs) induced cross reactive humoral and cellular response against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLMs, a murine model of progressive pulmonary TB was used. Animals immunized with PLMs with and without alum (PLMs/PLMsAL respectively) showed protection compared to non-immunized animals. Mice immunized with PLMsAL induced similar protection as that of BCG. Animals immunized with BCG, PLMs and PLMsAL showed a significant decrease in tissue damage (percentage of pneumonic area/lung) compared to non-immunized animals, with a more prominent effect in BCG vaccinated mice. The protective effect of the administration of PLMs in mice supports its future evaluation as experimental vaccine candidate against Mtb.

Evaluation of specific humoral immune response and cross reactivity against Mycobacterium tuberculosis antigens induced in mice immunized with liposomes composed of total lipids extracted from Mycobacterium smegmatis.

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.

Evaluation of the humoral immune response and cross reactivity against Mycobacterium tuberculosis of mice immunized with liposomes containing glycolipids of Mycobacterium smegmatis.

Mycobacterium smegmatis (Ms) is a nonpathogenic mycobacteria of rapid growth, which shares many characteristics with Mycobacterium tuberculosis (MTB), the major causative agent of tuberculosis. MTB has several cell wall glycolipids in common with Ms, which play an important role in the pathogenesis of tuberculosis and the induction of a protective immune response against MTB infection in some animal models. In this study, the humoral immune response and cross reactivity against MTB, of liposomes containing a mixture of cell wall glycolipids of Ms and commercial lipids was evaluated, in order to study its possible use as a component of a vaccine candidate against tuberculosis. Liposomes containing total lipids extracted from Ms, distearoyl phosphatidyl choline and cholesterol were prepared by the dehydration-rehydration technique. Balb/c mice were immunized with the liposomes obtained and the antibody response and cross reactivity against MTB were tested by ELISA. Total lipids extract from Ms showed the presence of several polar glycolipids in common with MTB, such as phosphatidylinositol mannosides. Liposomes that contained glycolipids of Ms were capable of inducing a specific IgG antibody response that allowed the recognition of surface antigens of MTB. The results of this study demonstrated the presence of immunogenic glycolipids in Ms, which could be included to enhance the protective effects of subunit vaccine formulations against tuberculosis.

Immunogenicity and cross-reactivity against Mycobacterium tuberculosis of proteoliposomes derived from Mycobacterium bovis BCG.

The only currently available vaccine against tuberculosis (TB) is Mycobacterium bovis Bacille Calmette-Guerin (BCG), which has inconsistent efficacy to protect against the disease in adults. M. tuberculosis (MTB) cell wall components have been implicated in the pathogenicity of TB and therefore have been a prime target for the identification and characterization of cell wall proteins with potential application in vaccine development. In this regard, proteoliposomes (PLs) derived from mycobacteria containing lipids and cell wall proteins could be potential vaccine candidates against TB. In the present study PLs derived from BCG were prepared. These homogeneous population of spherical microparticles was then immunized into Balb/c mice. Sera of immunized animals showed high IgG response and strong cross-reactivity against different MTB antigens.These results showed that BCG PLs could be potential vaccine candidates against TB.

Proteoliposomes from Mycobacterium smegmatis induce immune cross-reactivity against Mycobacterium tuberculosis antigens in mice.

Proteoliposomes (PL) obtained from Mycobacterium smegmatis (Ms) were evaluated for their capacity to elicit cross-reactive responses against Mycobacterium tuberculosis (Mtb) antigens in BALB/c mice. Animals immunized with PL adjuvanted with alum (PL-AL) or Freund's Incomplete Adjuvant (PL-IFA) showed significant IgG responses against the PL as well as total Ms lipids. Both groups of animals also showed significant IgG responses against BCG, but only animals immunized with PL-AL produced significant IgG responses against soluble cell wall proteins (SCWP) or whole cell lysate (WCL) of Mtb. Significant DTH responses against WCL were observed in both groups of animals after 24 h, but only PL-AL-immunized mice showed significant DTH responses after 48 h and 72 h. PL-Ms are capable of eliciting cross-reactive humoral and cellular responses against Mtb antigens and thus may be a potential vaccine strategy against tuberculosis.