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DOAJ Open Access 2025
Two Sides of the Same Coin—Mechanistic Insight, Diagnostic Application and Therapeutic Translation of Bacterial and Host‐Derived Extracellular Vesicles

Philipp Arnold, Fanni Annamária Boros, Jochen Mattner et al.

ABSTRACT Extracellular vesicles (EVs) have gained increasing attention in recent years due to their pivotal role in both health and disease. Emerging from both eukaryotic and prokaryotic cells, EVs serve as essential mediators of intercellular communication, exceeding the simplistic interactions observed with individual molecules. In this comprehensive review, we will focus on both Bacterial Extracellular Vesicles (BEV) and on Host derived Extracellular Vesicles (HEV) and highlight mechanistic principles, as well as their transformation into diagnostic and therapeutic tools. We will start with a short introduction into the biogenesis and principal properties of BEV and HEV. We will then focus on the composition of BEV and introduce OMICs‐based studies that helped to unravel their complex constitution. As both BEV and HEV interact with different epithelial and endothelial barriers and shape their properties, we will highlight mechanistic principles for both EV types. Starting from the intestinal system, where we will look at BEV and how these BEV overcome the intestinal barrier to change distant organs and the patient's immune system. We will then visit other endothelial and epithelial sites of the human body and summarize how HEV shapes these barriers and how HEV can overcome these barriers. We will then turn towards diagnostic and therapeutic approaches. As both BEV and HEV are currently suggested as diagnostic markers and are being investigated as potential therapeutic agents. Lastly, we will discuss current challenges and provide an outlook on the future in the field. This review seeks to raise awareness for both bacterial and host‐derived EVs, highlighting that they present two sides of the same coin.

DOAJ Open Access 2025
ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism

Christoffer Löf, Nasrin Sultana, Neha Goel et al.

Abstract Background Prostate cancer (PrCa) is a significant health concern, ranking as the second most common cancer in males globally. Genetic factors contribute substantially to PrCa risk, with up to 57% of the risk being attributed to genetic determinants. A major challenge in managing PrCa is the early identification of aggressive cases for targeted treatment, while avoiding unnecessary interventions in slow-progressing cases. Therefore, there is a critical need for genetic biomarkers that can distinguish between aggressive and non-aggressive PrCa cases. Previous research, including our own, has shown that germline variants in ANO7 are associated with aggressive PrCa. However, the function of ANO7 in the prostate remains unknown. Methods We performed RNA-sequencing (RNA-seq) on RWPE1 cells engineered to express ANO7 protein, alongside the analysis of a single-cell RNA-sequencing (scRNA-seq) dataset and RNA-seq from prostate tissues. Differential gene expression analysis and gene set enrichment analysis (GSEA) were conducted to identify key pathways. Additionally, we assessed oxidative phosphorylation (OXPHOS), glycolysis, and targeted metabolomics. Image analysis of mitochondrial morphology and lipidomics were also performed to provide further insight into the functional role of ANO7 in prostate cells. Results ANO7 expression resulted in the downregulation of metabolic pathways, particularly genes associated with the MYC pathway and oxidative phosphorylation (OXPHOS) in both prostate tissue and ANO7-expressing cells. Measurements of OXPHOS and glycolysis in the ANO7-expressing cells revealed a metabolic shift towards glycolysis. Targeted metabolomics showed reduced levels of the amino acid aspartate, indicating disrupted mitochondrial function in the ANO7-expressing cells. Image analysis demonstrated altered mitochondrial morphology in these cells. Additionally, ANO7 downregulated genes involved in fatty acid metabolism and induced changes in lipid composition of the cells, characterized by longer acyl chain lengths and increased unsaturation, suggesting a role for ANO7 in regulating lipid metabolism in the prostate. Conclusions This study provides new insights into the function of ANO7 in prostate cells, highlighting its involvement in metabolic pathways, particularly OXPHOS and lipid metabolism. The findings suggest that ANO7 may act as a key regulator of cellular lipid metabolism and mitochondrial function in the prostate, shedding light on a previously unknown aspect of ANO7’s biology.

Medicine, Cytology
DOAJ Open Access 2025
Combined Protein, Probiotics, and Exercise Therapy for Sarcopenia: A Comprehensive Review

Ryuk Jun Kwon, Mohammad Al Mijan, Soo Min Son et al.

Sarcopenia, a progressive loss of muscle mass and strength, is a major health concern primarily affecting older adults worldwide. With no pharmaceutical cure for sarcopenia, dietary protein, probiotic supplementation, and physical exercise have gained increasing attention as lifestyle-based interventions. Dietary protein has shown promising effects in preventing the loss of skeletal muscle and physical strength by favorably influencing muscle protein synthesis in sarcopenic individuals. Probiotic supplementation has been associated with muscle regeneration, increased muscle protein synthesis among adults with sarcopenia, and improved exercise performance based on preliminary and emerging evidence. Multimodal or hybrid exercise programs have been shown to improve muscle strength, mobility, and overall physical function in individuals with sarcopenia. This paper reviews how combining protein, probiotics, and multimodal exercise may offer complementary strategies for sarcopenia management. Evidence from preclinical and mechanistic studies suggests that these interventions may support muscle health by activating shared intracellular pathways such as mTOR signaling, the suppression of FOXO3a, and the enhancement of mitochondrial biogenesis.

DOAJ Open Access 2024
Pharmacology of LRRK2 with type I and II kinase inhibitors revealed by cryo-EM

Hanwen Zhu, Patricia Hixson, Wen Ma et al.

Abstract LRRK2 is one of the most promising drug targets for Parkinson’s disease. Though type I kinase inhibitors of LRRK2 are under clinical trials, alternative strategies like type II inhibitors are being actively pursued due to the potential undesired effects of type I inhibitors. Currently, a robust method for LRRK2–inhibitor structure determination to guide structure-based drug discovery is lacking, and inhibition mechanisms of available compounds are also unclear. Here we present near-atomic-resolution structures of LRRK2 with type I (LRRK2-IN-1 and GNE-7915) and type II (rebastinib, ponatinib, and GZD-824) inhibitors, uncovering the structural basis of LRRK2 inhibition and conformational plasticity of the kinase domain with molecular dynamics (MD) simulations. Type I and II inhibitors bind to LRRK2 in active-like and inactive conformations, so LRRK2–inhibitor complexes further reveal general structural features associated with LRRK2 activation. Our study provides atomic details of LRRK2–inhibitor interactions and a framework for understanding LRRK2 activation and for rational drug design.

DOAJ Open Access 2024
Association of Regular Cervical Cancer Screening with Socioeconomic, COVID-19 Infection and Vaccine Status Among Japanese Population: Cohort Observational Study

Mitoma T, Maki J, Ooba H et al.

Tomohiro Mitoma,1 Jota Maki,1 Hikaru Ooba,1 Chikako Ogawa,1 Hisashi Masuyama,1 Takahiro Tabuchi2 1Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan; 2Department of Cancer Control Center, Osaka International Cancer Institute, Osaka, JapanCorrespondence: Jota Maki, Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan, Tel +81-86-235-7320, Fax +81-86-225-9570, Email jotamaki@okayama-u.ac.jpPurpose: Among the Organisation for Economic Co-operation and Development countries, Japan has one of the lowest cervical cancer screening coverages. Cancer screening coverage has worsened due to the coronavirus disease of 2019 (COVID-19) pandemic. This study investigated the relationship between socioeconomic background, COVID-19 infection history and vaccine status, and regular cervical cancer screening (CCS) during the two years of the COVID-19 era in Japan.Patients and Methods: We used data from the Japan COVID-19 and Society Internet Survey, a nationwide, Internet-based, self-report cohort observational study conducted in 2022. The outcome variable was identified by asking whether the participants had undergone CCS within the last two years. Cervical cytology was performed in Japan by brushing the external cervical os. This study used multivariate log-binomial regression models to evaluate inequalities during regular checkups for CCS. Adjusted prevalence ratios (APRs) with 95% confidence intervals (CIs) were estimated to incorporate the socioeconomic background variables.Results: Of the 12,066 participants, 5597 (46.4%) had undergone regular CCS for over two years. The prevalence ratio (PR) of patients who underwent CCS was 0.70 for those in their 20s and 0.78 for those in their 60s, compared to those in their 40s. Socioeconomic inequities were found in the following groups: unemployed/student, unmarried, high school graduate or lower, and household income below 4 million Yen. Our final multivariate analysis revealed that participants who were in their 20s or 60s, had a household income below 4 million Yen, were unmarried, had no annual health check-ups, and were unvaccinated with COVID-19 were at a higher risk of not undergoing CCS.Conclusion: The relationship between socioeconomic inequality and CCS hesitancy is prevalent among younger participants. The CCS coverage in Japan during the COVID-19 pandemic year (2020– 2022) was not low compared with the pre-pandemic era.Keywords: cervical cancer screening, social inequality, screening hesitation, internet survey

Medicine (General)
DOAJ Open Access 2024
The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

Asal Barshidi, Keivan Ardeshiri, Farbod Ebrahimi et al.

Abstract The immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses. The suppression of NK cells in various cancers can lead to the induction of an exhausted phenotype in NK cells, which will impair their function. Recent studies have shown that the occurrence of this phenotype in various types of leukemic malignancies can affect the prognosis of the disease, and targeting these cells may be considered a new immunotherapy method in the treatment of leukemia. Therefore, a detailed study of exhausted NK cells in leukemic diseases can help both to understand the mechanisms of leukemia progression and to design new treatment methods by creating a deeper understanding of these cells. Here, we will comprehensively review the immunobiology of exhausted NK cells and their role in various leukemic malignancies. Video Abstract

Medicine, Cytology
DOAJ Open Access 2024
Topography of the mandibular canal in male human skulls originating from different time periods

Aleksandra Gawlikowska-Sroka, Łukasz Stocki, Jacek Szczurowski et al.

BACKGROUND: Dynamic advances in dentistry, especially in implantology has inspired researchers to carry out many studies investigating the topography of the mandibular canal and its ethnic differences. The aim of the study was a comparative analysis of variations in the position and topography of the mandibular canal based on radiographic images of human mandibles originating from modern and medieval skulls. MATERIALS AND METHODS: Morphometric examination of 126 radiographs of skulls (92 modern and 34 medieval skulls) was included. The age and sex of individuals were determined based on the morphology of the skull, the obliteration of cranial sutures, and the degree of tooth wear. To define the topography of the mandibular canal on X-ray images, we took 8 anthropometric measurements. RESULTS: We observed significant differences in several parameters. The distance between the base of the mandible and the bottom of the mandibular canal, the distance between the top of the mandibular canal and the crest of the alveolar arch, and the height of the mandibular body. Significant asymmetry was found for two parameters of mandibles from modern skulls: the distance between the top of the mandibular canal and the crest of the alveolar arch at the level of the second molar (p < 0.05), and the distance between the mandibular foramen and the margin of the anterior mandibular ramus (p < 0.007). There were no significant differences between measurements taken on the right and left sides of the medieval skulls. CONCLUSIONS: Our study revealed differences in the position of the mandibular canal between modern and medieval skulls, confirming the presence of geographical and chronological differences between populations. Knowledge of variability in the position of the mandibular canal between different local populations is fundamental for the correct interpretation of findings from diagnostic radiological studies used in dental practice and in forensic odontology or analysis of archaeological bone materials.

Human anatomy, Cytology
DOAJ Open Access 2024
Branch-duct intraductal papillary mucinous neoplasm: a retrospective study on neoplastic risk after 5 years of surveillance

Marie-Pier Bachand, Mohamed-Anas Chennouf, Mandy Malick et al.

Objectives:. Long-term surveillance of branch-duct intraductal papillary mucinous neoplasms (BD-IPMN) remains controversial, particularly regarding cysts follow-up >5 years. The primary endpoint of this study was to assess the risk of malignant transformation of presumed BD-IPMN during follow-up and identify clinical and morphological predictors of malignancy. Methods:. We performed a retrospective analysis of data from all patients with a presumed BD-IPMN diagnosis at the CIUSSS de l’Estrie CHUS, from 2004 to 2018. Results:. The final database included 380 patients with presumed BD-IPMN with a median follow-up of 43.9 months (interquartile range [IQR] 28.6–73.3 months). Mean age at diagnosis was 65.5 years [27–90], 159 patients (42.8%) were male and 17 patients (4.5%) underwent resection of their lesion during their surveillance period. In our cohort, 132 patients (34.7%) had a follow-up of >5 years. Overall risk of malignancy was 2.1% [0.9%–4.1%]. During follow-up, neoplastic transformation was observed in 2 of 132 patients (1.5%) surveilled >5 years. Malignancy was significantly associated with cyst growth >2.5 mm/y (57.1% vs 5.8%; P < .001) dilated MPD (71.4% vs 4.9%; P < .001), solid component (71.4% vs 1.3%; P < .001), positive cytology (37.5% vs 0.5%; P < .001), development of high-risk stigmatas (87.5% vs 1.9%; P < .001), or worrisome features (87.5% vs 23.9%; P < .001) during follow-up and symptoms of jaundice (25% vs 0.5%; P = .002) and abdominal pain (50% vs 9.4%; P = .005). Conclusion:. While overall malignancy risk remains low in presumed BD-IPMN, continuous surveillance should be pursued after 5 years in surgically fit individuals, particularly in patients who develop our identified risk factors.

Diseases of the digestive system. Gastroenterology
DOAJ Open Access 2022
RSL1D1 promotes the progression of colorectal cancer through RAN-mediated autophagy suppression

Xunhua Liu, Jianxiong Chen, Xiaoli Long et al.

Abstract RSL1D1 (ribosomal L1 domain containing 1), a member of the universal ribosomal protein uL1 family, was suggested to be a new candidate target for colorectal cancer (CRC). However, the role of RSL1D1 in cancer, including CRC, remains largely elusive. Here, we demonstrated that RSL1D1 expression was significantly elevated in tumors from CRC patients and that high expression of RSL1D1 was correlated with poorer survival of CRC patients. Functionally, RSL1D1 promoted the proliferation, invasion, and metastasis of CRC cells by suppressing autophagy. Interestingly, RSL1D1 interacted with RAN and inhibited its deacetylation by competitively binding with Sirt7. By affecting the acetylation of RAN, RSL1D1 inhibited the accumulation of nuclear STAT3 and the STAT3-regulated autophagic program. Taken together, our study uncovered the key role of the RSL1D1/RAN/STAT3 regulatory axis in autophagy and tumor progression in CRC, providing a new candidate target for CRC treatment.

DOAJ Open Access 2022
The Role of ATR Inhibitors in Ovarian Cancer: Investigating Predictive Biomarkers of Response

Alice Bradbury, Frank T. Zenke, Nicola J. Curtin et al.

Ataxia telangiectasia and Rad-3 related kinase (ATR) signals DNA lesions and replication stress (RS) to the S and G2/M checkpoints and DNA repair pathways making it a promising target to exploit the dysregulated DNA damage response in cancer. ATR inhibitors (ATRi) are under clinical investigation as monotherapy and in combination with other anticancer agents. Molecular determinants of sensitivity to ATRi are common in ovarian cancer, suggesting the therapeutic potential of ATRi. We investigated the cytotoxicity of the ATRi, VE-821, in a panel of human ovarian cancer cell lines. High grade serous (HGS) cell lines were significantly more sensitive to VE-821 than non-HGS (<i>p</i> ≤ 0.0001) but previously identified determinants of sensitivity (<i>TP53</i>, <i>ATM</i> and <i>BRCA1</i>) were not predictive. Only low RAD51 (<i>p</i> = 0.041), TopBP1 (<i>p</i> = 0.026) and APOBEC3B (<i>p</i> = 0.015) protein expression were associated with increased VE-821 sensitivity. HGS cells had increased levels of RS (pRPA<sup>Ser4/8</sup> and γH2AX nuclear immunofluorescence), and elevated RS predicted sensitivity to VE-821 independently of the cell line subtype. These data suggest that functional assessment of RS biomarkers may be a better predictive biomarker of ATRi response than any single aberrant gene in ovarian cancer and potentially other cancers.

DOAJ Open Access 2021
Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway

Li-Xin Ren, Jin-Chun Qi, An-Ning Zhao et al.

Abstract Background The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. Methods MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules. Results MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression. Conclusion These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC.

Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cytology
DOAJ Open Access 2020
CRISPR-Mediated Base Conversion Allows Discriminatory Depletion of Endogenous T Cell Receptors for Enhanced Synthetic Immunity

Roland Preece, Andrea Pavesi, Soragia Athina Gkazi et al.

Emerging base editing technology exploits CRISPR RNA-guided DNA modification effects for highly specific C > T conversion, which has been used to efficiently disrupt gene expression. These tools can enhance synthetic T cell immunity by restricting specificity, addressing histocompatibility leukocyte antigen (HLA) barriers, and promoting persistence. We report lentiviral delivery of a hepatitis B-virus (HBV)-specific recombinant T cell receptor (rTCR) and a linked CRISPR single-guide RNA for simultaneous disruption of endogenous TCRs (eTCRs) when combined with transient cytosine deamination. Discriminatory depletion of eTCR and coupled expression of rTCR resulted in enrichment of HBV-specific populations from 55% (SEM, ±2.4%) to 95% (SEM, ±0.5%). Intensity of rTCR expression increased 1.8- to 2.9-fold compared to that in cells retaining their competing eTCR, and increased cytokine production and killing of HBV antigen-expressing hepatoma cells in a 3D microfluidic model were exhibited. Molecular signatures confirmed that seamless conversion of C > T (G > A) had created a premature stop codon in TCR beta constant 1/2 loci, with no notable activity at predicted off-target sites. Thus, targeted disruption of eTCR by cytosine deamination and discriminatory enrichment of antigen-specific T cells offers the prospect of enhanced, more specific T cell therapies against HBV-associated hepatocellular carcinoma (HCC) as well as other viral and tumor antigens.

Genetics, Cytology
DOAJ Open Access 2020
<i>shp-2</i> gene knockout upregulates CAR-driven cytotoxicity of YT NK cells

V. G. Subrakova, S. V. Kulemzin, T. N. Belovezhets et al.

In Russia, cancer is the second leading cause of death following cardiovascular diseases. Adoptive transfer of NK cells is a promising approach to fight cancer; however, for their successful use in cancer treatment, it is necessary to ensure their robust accumulation at tumor foci, provide resistance to the immunosuppressive tumor microenvironment, and to engineer them with higher cytotoxic activity. NK lymphocytes are known to kill cancer cells expressing a number of stress ligands; and the balance of signals from inhibitory and activating receptors on the surface of the NK cell determines whether a cytotoxic reaction is triggered. We hypothesized that stronger cytotoxicity of NK cells could be achieved via gene editing aimed at enhancing the activating signaling cascades and/or weakening the inhibitory ones, thereby shifting the balance of signals towards NK cell activation and target cell lysis. Here, we took advantage of the CRISPR/Cas9 system to introduce mutations in the coding sequence of the shp-2 (PTPN11) gene encoding the signaling molecule of inhibitory pathways in NK cells. These shp-2 knock-out NK cells were additionally transduced to express a chimeric antigen receptor (CAR) that selectively recognized the antigen of interest on the target cell surface and generated an activating signal. We demonstrate that the combination of shp-2 gene knockout and CAR expression increases the cytotoxicity of effector NK-like YT cells against human prostate cancer cell line Du-145 with ectopic expression of PSMA protein, which is specifically targeted by the CAR.

DOAJ Open Access 2020
Cellular Response to Vitamin C-Enriched Chitosan/Agarose Film with Potential Application as Artificial Skin Substitute for Chronic Wound Treatment

Vladyslav Vivcharenko, Michal Wojcik, Agata Przekora

The treatment of chronic wounds is still a meaningful challenge to physicians. The aim of this work was to produce vitamin C-enriched chitosan/agarose (CHN/A) film that could serve as potential artificial skin substitute for chronic wound treatment. The biomaterial was fabricated by a newly developed and simplified method via mixing acidic chitosan solution with alkaline agarose solution that allowed to obtain slightly acidic pH (5.97) of the resultant material, which is known to support skin regeneration. Vitamin C was immobilized within the matrix of the film by entrapment method during production process. Produced films (CHN/A and CHN/A + vit C) were subjected to comprehensive evaluation of cellular response with the use of human skin fibroblasts, epidermal keratinocytes, and macrophages. It was demonstrated that novel biomaterials support adhesion and growth of human skin fibroblasts and keratinocytes, have ability to slightly reduce transforming growth factor-beta 1 (TGF-β1) (known to be present at augmented levels in the epidermis of chronic wounds), and increase platelet-derived growth factor-BB (PDGF-BB) secretion by the cells. Nevertheless, addition of vitamin C to the biomaterial formulation does not significantly improve its biological properties due to burst vitamin release profile. Obtained results clearly demonstrated that produced CHN/A film has great potential to be used as cellular dermal, epidermal, or dermo-epidermal graft pre-seeded with human skin cells for chronic wound treatment.

DOAJ Open Access 2020
The Art and Science of Selecting a CD123-Specific Chimeric Antigen Receptor for Clinical Testing

Janice M. Riberdy, Sheng Zhou, Fei Zheng et al.

Chimeric antigen receptor (CAR) T cells targeting CD123, an acute myeloid leukemia (AML) antigen, hold the promise of improving outcomes for patients with refractory/recurrent disease. We generated five lentiviral vectors encoding CD20, which may serve as a target for CAR T cell depletion, and 2nd or 3rd generation CD123-CARs since the benefit of two costimulatory domains is model dependent. Four CARs were based on the CD123-specific single-chain variable fragment (scFv) 26292 (292) and one CAR on the CD123-specific scFv 26716 (716), respectively. We designed CARs with different hinge/transmembrane (H/TM) domains and costimulatory domains, in combination with the zeta (z) signaling domain: 292.CD8aH/TM.41BBz (8.41BBz), 292.CD8aH/TM.CD28z (8.28z), 716.CD8aH/TM.CD28z (716.8.28z), 292.CD28H/TM. CD28z (28.28z), and 292.CD28H/TM.CD28.41BBz (28.28.41BBz). Transduction efficiency, expansion, phenotype, and target cell recognition of the generated CD123-CAR T cells did not significantly differ. CAR constructs were eliminated for the following reasons: (1) 8.41BBz CARs induced significant baseline signaling, (2) 716.8.28z CAR T cells had decreased anti-AML activity, and (3) CD28.41BBz CAR T cells had no improved effector function in comparison to CD28z CAR T cells. We selected the 28.28z CAR since CAR expression on the cell surface of transduced T cells was higher in comparison to 8.28z CARs. The clinical study (NCT04318678) evaluating 28.28z CAR T cells is now open for patient accrual.

Genetics, Cytology
DOAJ Open Access 2019
Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt pathway, Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development

Pietro Gentile, Simone Garcovich

The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (&#946;-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).

DOAJ Open Access 2018
Oropharynx HPV status and its relation to HIV infection

Leonora Maciel de Souza Vianna, Fabiana Pirani Carneiro, Rivadavio Amorim et al.

Background The number of oropharyngeal lesions caused by HPV (Human papillomavirus) has been increasing worldwide in the past years. In spite of the clinical relevance of HPV infection in the anogenital tract of HIV-positive patients, the relevance of oropharynx HPV infection in these patients is not clear. The aim of the present study was to detect HPV infection, and clinical and cytological changes in the oropharynx of HIV-positive patients. Methods Samples collected from the oropharynx of 100 HIV-positive patients were subjected to hybrid capture (HC), conventional and liquid-based cytology. Clinical data were also collected to investigate the relation with HPV status. Results High and low-risk types of HPV were present in 8% and 16.7% of the total sample. The mean ± sd (maximum-minimum) of the relative ratio light unit (RLU)/cutoff (CO) was 2.94 ± 2.58 (1.09–7.87) and 1.61 ± 0.65 (1.07–2.8) for high- and low-risk-HPV, respectively. By cytology, dysplasia was not detected, but atypical squamous cells of undetermined significance (ASC-US) were diagnosed in two samples. No clinical change, suggestive of dysplasia/cancer, was detected. Conclusion Our study was able to detect and characterize HPV infection by hybrid capture, which may represent a good tool for screening and follow-up of HPV in the studied population. The frequency and viral load of HPV were low. Neither clinical nor cytological changes suggestive of dysplasia/neoplasia were observed in oropharynx of HIV-positive patients.

Medicine, Biology (General)

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