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Physiological and pathological functions of βB2-crystallins in multiple organs: a systematic review.Aging Jun 2021Crystallins, the major constituent proteins of mammalian lenses, are significant not only for the maintenance of eye lens stability, transparency, and refraction, but...
Crystallins, the major constituent proteins of mammalian lenses, are significant not only for the maintenance of eye lens stability, transparency, and refraction, but also fulfill various physiopathological functions in extraocular tissues. βB2-crystallin, for example, is a multifunctional protein expressed in the human retina, brain, testis, ovary, and multiple tumors. Mutations in the βB2 crystallin gene or denaturation of βB2-crystallin protein are associated with cataracts, ocular pathologies, and psychiatric disorders. A prominent role for βB2-crystallins in axonal growth and regeneration, as well as in dendritic outgrowth, has been demonstrated after optic nerve injury. Studies in βB2-crystallin-null mice revealed morphological and functional abnormalities in testis and ovaries, indicating βB2-crystallin contributes to male and female fertility in mice. Interestingly, although pathogenic significance remains obscure, several studies identified a clear correlation between βB2 crystallin expression and the prognosis of patients with breast cancer, colorectal cancer, prostate cancer, renal cell carcinoma, and glioblastoma in the African American population. This review summarizes the physiological and pathological functions of βB2-crystallin in the eye and other organs and tissues and discusses findings related to the expression and potential role of βB2-crystallin in tumors.
Topics: Black or African American; Humans; Lens, Crystalline; Neoplasms; Organ Specificity; beta-Crystallin B Chain
PubMed: 34118792
DOI: 10.18632/aging.203147 -
Cureus Sep 2022Asthma is a non-communicable and long-term condition affecting children and adults. The air passages in the lungs become narrow due to inflammation and tightening of the... (Review)
Review
Asthma is a non-communicable and long-term condition affecting children and adults. The air passages in the lungs become narrow due to inflammation and tightening of the muscles around the small airways. Symptoms of asthma are intermittent and include cough, wheeze, shortness of breath, and chest tightness. Asthma is very often underdiagnosed and under-treated in many regions, especially in developing countries. While many studies show that viral infections can precipitate asthmatic attacks, very few studies have been conducted to see if history or current asthmatic attack increases the risk of viral infections. Our study aims to determine the predisposition of asthmatics to develop various viral infections and susceptibility toward certain viruses that cause upper respiratory tract infections. We performed a literature review of both published and unpublished articles. We included case reports, case series, reviews, clinical trials, cohort, and case-control studies, written only in English. Commentaries, letters to editors, and book chapters were excluded. Our initial search yielded 948 articles, of which 826 were rejected either because they were irrelevant or because they did not meet our inclusion criteria. We finally screened 122 abstracts and identified 24 relevant articles. People with a history of asthma have an abnormal innate immune response, making them potentially slower in clearing the infection and susceptible to both infections and virus-induced cell cytotoxicity. Also, in these studies, deficiencies in the interferon alpha response of peripheral blood mononuclear cells and plasmacytoid dendritic cells have been observed in asthmatics, both adults and children. Asthmatics with a viral infection usually present with an acute exacerbation of asthma, represented by dyspnea and cough, with other prodromal symptoms including vomiting and general malaise. The review includes an update on the relevance of dysregulated immune pathways in causing viral infections in asthmatic populations. It focuses on the evidence to suggest that people with asthma are at increased risk of viral infection, and viral infections in turn are known to precipitate and worsen the asthmatic status, making this a vicious cycle. The authors also suggest that further studies be undertaken to elucidate the pathophysiology and identify the critical therapeutic steps to break this vicious cycle and improve the quality of life for people with asthma.
PubMed: 36225449
DOI: 10.7759/cureus.28839 -
Journal of Experimental & Clinical... Jun 2021Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological... (Review)
Review
Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological complexities surrounding glioblastoma, lymphocytes that infiltrate the brain to develop durable immunity with memory will be key. Polyinosinic:polycytidylic acid, or poly(I:C), and its derivative poly-ICLC could serve as a priming or boosting therapy to unleash lymphocytes and other factors in the (immuno)therapeutic armory against glioblastoma. Here, we present a systematic review on the effects and efficacy of poly(I:C)/poly-ICLC for glioblastoma treatment, ranging from preclinical work on cellular and murine glioblastoma models to reported and ongoing clinical studies. MEDLINE was searched until 15 May 2021 to identify preclinical (glioblastoma cells, murine models) and clinical studies that investigated poly(I:C) or poly-ICLC in glioblastoma. A systematic review approach was conducted according to PRISMA guidelines. ClinicalTrials.gov was queried for ongoing clinical studies. Direct pro-tumorigenic effects of poly(I:C) on glioblastoma cells have not been described. On the contrary, poly(I:C) changes the immunological profile of glioblastoma cells and can also kill them directly. In murine glioblastoma models, poly(I:C) has shown therapeutic relevance as an adjuvant therapy to several treatment modalities, including vaccination and immune checkpoint blockade. Clinically, mostly as an adjuvant to dendritic cell or peptide vaccines, poly-ICLC has been demonstrated to be safe and capable of eliciting immunological activity to boost therapeutic responses. Poly-ICLC could be a valuable tool to enhance immunotherapeutic approaches for glioblastoma. We conclude by proposing several promising combination strategies that might advance glioblastoma immunotherapy and discuss key pre-clinical aspects to improve clinical translation.
Topics: Animals; Brain Neoplasms; Cancer Vaccines; Carboxymethylcellulose Sodium; Clinical Trials as Topic; Glioblastoma; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Mice; Poly I-C; Polylysine
PubMed: 34172082
DOI: 10.1186/s13046-021-02017-2 -
Frontiers in Immunology 2020Camels are domesticated animals that are highly adapted to the extreme desert ecosystem with relatively higher resistance to a wide range of pathogens compared to many...
Camels are domesticated animals that are highly adapted to the extreme desert ecosystem with relatively higher resistance to a wide range of pathogens compared to many other species from the same geographical region. Recently, there has been increased interest in the field of camel immunology. As the progress in the analysis of camel immunoglobulins has previously been covered in many recent reviews, this review intends to summarize published findings related to camel cellular immunology with a focus on the phenotype and functionality of camel leukocyte subpopulations. The review also describes the impact of different physiological (age and pregnancy) and pathological (e.g. infection) conditions on camel immune cells. Despite the progress achieved in the field of camel immunology, there are gaps in our complete understanding of the camel immune system. Questions remain regarding innate recognition mechanisms, the functional characterization of antigen-presenting cells, and the characterization of camel NK and cytotoxic T cells.
Topics: Aging; Animals; Animals, Newborn; Camelus; Communicable Diseases; Female; Immunity, Mucosal; Leukocytes; Monocytes; Neutrophils; Pregnancy
PubMed: 33569060
DOI: 10.3389/fimmu.2020.614150 -
Future Oncology (London, England) Mar 2023Blastic plasmacytoid dendritic cell neoplasm is a rarely occurring hematologic malignancy with a dismal prognosis. We conducted a meta-analysis for a total of 1312... (Meta-Analysis)
Meta-Analysis Review
Blastic plasmacytoid dendritic cell neoplasm is a rarely occurring hematologic malignancy with a dismal prognosis. We conducted a meta-analysis for a total of 1312 patients from 24 retrospective studies. The complete remission (CR) rate of acute lymphoblastic leukemia-like induction chemotherapy was 82%, and the overall survival (OS) was 15.75 months; the CR rate of acute myeloid leukemia-like chemotherapy was 51%, and the OS was 7.18 months; and the CR rate of cyclophosphamide, doxorubicin, vincristine and prednisone-like chemotherapy was 50%, and the OS was 12.06 months. Acute lymphoblastic leukemia-like induction chemotherapy has the best CR rate and OS.
Topics: Humans; Induction Chemotherapy; Retrospective Studies; Hematologic Neoplasms; Acute Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myeloproliferative Disorders; Dendritic Cells
PubMed: 36919853
DOI: 10.2217/fon-2022-0521 -
Frontiers in Medicine 2021To conduct a systematic review and meta-analysis of the available research on evaluating changes in corneal dendritic cell density (CDCD) and the main subbasal nerve...
To conduct a systematic review and meta-analysis of the available research on evaluating changes in corneal dendritic cell density (CDCD) and the main subbasal nerve parameters (SNPs) on the ocular surface and assessing the diagnostic performance of confocal microscopy in patients with dry eye disease. A computerized systematic review of literature published in PUBMED, EMBASE, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials until May 8, 2020 was performed. All statistical analyses were conducted in software. The weighted mean differences (WMDs) and standardized mean differences (SMDs) with 95% confidence intervals (CI) between dry eye patients and healthy subjects were presented as results. A total of 11 studies with 755 participants were recruited, and 931 eyes were included in this meta-analysis. However, not all studies reported both CDCD and SNPs. CDCD in the central cornea was higher (WMD = 51.06, 95% CI = 39.42-62.71), while corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) were lower (WMD = -7.96, 95% CI = -12.12 to -3.81; SMD = -2.30, 95%CI = -3.26 to -1.35) in dry eye patients in comparison with the corresponding values in healthy controls (all < 0.00001). Taken together, while CNFD and CNFL were lower in dry eye patients, central CDCD showed a significant increase in these patients in comparison with the corresponding values in healthy controls.
PubMed: 33898473
DOI: 10.3389/fmed.2021.578233 -
The Journal of Surgical Research Jun 2024Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging... (Review)
Review
INTRODUCTION
Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance.
METHODS
Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization.
RESULTS
Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αβ-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance.
CONCLUSIONS
Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.
PubMed: 38851085
DOI: 10.1016/j.jss.2024.04.079 -
Clinical Nutrition ESPEN Feb 2023Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity. (Review)
Review
BACKGROUND
Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity.
OBJECTIVE
Therefore, this systematic review aimed to evaluate antitumor and chemopreventive activity of different vitamin E isoforms (tocopherols and tocotrienols) through in vitro and in vivo studies.
METHOD
The systematic review was registered in PROSPERO (No. CRD4202126207) and the search was carried out in four electronic databases (PubMed, Science Direct, Scopus and Web of Science) in June 2021 by three independent reviewers. The search equation used was: "Supplementation" AND ("Vitamin E" OR Tocopherol OR Tocotrienol) AND "breast cancer" AND (chemotherapy OR therapy OR prevention). In vitro studies and animal models of breast cancer supplemented with tocopherol or tocotrienol vitamers, alone or in combination, were included.
RESULTS
The results revealed 8546 relevant studies that were initially identified in our search. After analysis, a total of 12 studies were eligible for this systematic review. All studies included animal models, and 5 of them also performed in vitro experiments on cancer cell lines. The studies performed supplementation with tocopherols, mixtures (tocopherols and tocotrienols) and synthetic vitamin E forms. There was an significant association of estradiol, dendritic cells and pterostilbene in combined therapy with vitamin E. Vitamin E delayed tumor development, reduced tumor size, proliferation, viability, expression of anti-apoptotic and cell proliferation genes, and upregulated pro-apoptotic genes, tumor suppressor genes and increased immune response. The effects on oxidative stress markers and antioxidant activity were conflicting among studies. Only one study with synthetic vitamin E reported cardiotoxicity, but it did not show vitamin E genotoxicity.
CONCLUSION
In conclusion, vitamin E isoforms, isolated or associated, showed antitumor and chemopreventive activity. However, due to studies heterogeneity, there is a need for further analysis to establish dose, form, supplementation time and breast cancer stage.
Topics: Animals; Vitamin E; Tocotrienols; Antioxidants; Tocopherols; Neoplasms; Vitamins
PubMed: 36657931
DOI: 10.1016/j.clnesp.2022.11.001 -
Frontiers in Immunology 2021Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and...
Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and chemoprevention remain the main risk-reducing modalities for those with hereditary cancer syndromes, as well as high-risk non-hereditary breast lesions such as ADH, ALH, or LCIS. Ductal carcinoma (DCIS) is a preinvasive malignant lesion of the breast that closely mirrors IBC and, if left untreated, develops into IBC in up to 50% of lesions. Certain high-risk patients with DCIS may have a 25% risk of developing recurrent DCIS or IBC, even after surgical resection. The development of breast cancer elicits a strong immune response, which brings to prominence the numerous advantages associated with immune-based cancer prevention over drug-based chemoprevention, supported by the success of dendritic cell vaccines targeting HER2-expressing BC. Vaccination against BC to prevent or interrupt the process of BC development remains elusive but is a viable option. Vaccination to intercept preinvasive or premalignant breast conditions may be possible by interrupting the expression pattern of various oncodrivers. Growth factors may also function as potential immune targets to prevent breast cancer progression. Furthermore, neoantigens also serve as effective targets for interception by virtue of strong immunogenicity. It is noteworthy that the immune response also needs to be strong enough to result in target lesion elimination to avoid immunoediting as it may occur in IBC arising from DCIS. Overall, if the issue of vaccine targets can be solved by interrupting premalignant lesions, there is a potential to prevent the development of IBC.
Topics: Animals; Antigens, Neoplasm; Breast Carcinoma In Situ; Breast Neoplasms; Cancer Vaccines; Carcinoma, Intraductal, Noninfiltrating; Disease Progression; Female; Humans; Neoplasm Invasiveness; Precancerous Conditions; Tumor Microenvironment; Vaccination
PubMed: 34899753
DOI: 10.3389/fimmu.2021.786286 -
International Journal of Molecular... Sep 2021The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells,...
The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.
Topics: Cell Degranulation; Cornea; Extracellular Traps; Eye Diseases; Humans; Neutrophil Infiltration; Neutrophils
PubMed: 34638724
DOI: 10.3390/ijms221910386