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The diagnosis and identification of melanoma are not always accurate, even for experienced dermatologists. Histopathology continues to be the gold standard, assessing specific parameters such as the Breslow index. However, it remains invasive and may lack effectiveness. Therefore, leveraging mathematical modeling and informatics has been a pursuit of diagnostic methods favoring early detection. Fractality, a mathematical parameter quantifying complexity and irregularity, has proven useful in melanoma diagnosis. Nonetheless, no studies have implemented this metric to feed artificial intelligence algorithms for the automatic classification of dermatological lesions, including melanoma. Hence, this study aimed to determine the combined utility of fractal dimension and unsupervised low-computational-requirements machine learning models in classifying melanoma and non-melanoma lesions. We analyzed 39,270 dermatological lesions obtained from the International Skin Imaging Collaboration. Box-counting fractal dimensions were calculated for these lesions. Fractal values were used to implement classification methods by unsupervised machine learning based on principal component analysis and iterated K-means (100 iterations). A clear separation was observed, using only fractal dimension values, between benign or malignant lesions (sensibility 72.4% and specificity 50.1%) and melanoma or non-melanoma lesions (sensibility 72.8% and specificity 50%) and subsequently, the classification quality based on the machine learning model was ≈80% for both benign and malignant or melanoma and non-melanoma lesions. However, the grouping of metastatic melanoma versus non-metastatic melanoma was less effective, probably due to the small sample size included in MM lesions. Nevertheless, we could suggest a decision algorithm based on fractal dimension for dermatological lesion discrimination. On the other hand, it was also determined that the fractal dimension is sufficient to generate unsupervised artificial intelligence models that allow for a more efficient classification of dermatological lesions.

Background and Objectives : Leukemia, characterized by abnormal leukocyte production, exhibits clonal origin from somatic mutations. Globally, it ranked 15th in cancer incidence in 2020, with higher prevalence in developing countries. In Mexico, it was the ninth most frequent cancer. Regional registries are vital for understanding its epidemiology. This study aims to analyze the prevalence and age-standardized incidence rates of leukemias in a tertiary care hospital in the Mexican Bajio region. Materials and Methods : Leukemia cases from 2008-2018 were analyzed, and 535 medical records were included in this study. The prevalence, distribution, and age-specific incidence rate of different types and subtypes of leukemia were determined according to sex and age groups. Results : Overall, 65.79% consisted of lymphocytic leukemia, 33.64% of myeloid leukemia, and 0.56% of monocytic leukemia. No significant sex-based differences were found, but age-specific patterns were observed. Leukemia distribution by age revealed significant associations. Lymphocytic leukemia dominated in the pediatric population, particularly acute lymphocytic leukemia, while myeloid leukemia shifted towards adulthood. Age-specific incidence patterns showed, first, that lymphocytic leukemia is the most common leukemia in pediatric ages, and second, there is a shift from acute lymphocytic leukemia dominance in pediatric ages to myeloid leukemia incidence in late adulthood, emphasizing nuanced epidemiological dynamics. Conclusions : Acute leukemia cases occurred with high prevalence in our study population, with a high incidence in pediatric and adulthood populations, especially for acute lymphocytic leukemia, showing a (<18 years) 153.8 age-standardized incidence rate in the pediatric group, while in the adult population, the age-standardized rate was 59.84. In the age-specific analysis, we found that the childhood group (5-9 years) were the most affected by acute lymphocytic leukemia in the pediatric population, while in the adult population, the early-adulthood group (15-29 years) were the most affected age group. In contrast, chronic myeloid leukemia affected both adults and the pediatric populations, while chronic lymphocytic leukemia and monocytic leukemia were exclusive to adults. The study underscores the need for tailored diagnostic, treatment, and preventive strategies based on age, contributing valuable insights into the leukemia epidemiology of the Bajio region.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the presence of the Philadelphia chromosome, a product of the reciprocal translocation t(9;22)(q34;q11), in the BCR and ABL genes. These rearrangements in both genes lead to the formation of various fusion mRNA products, with preferential expression of b2a2 , b3a2 , and other BCR::ABL1 mRNA variants, combined with additional chromosomal abnormalities. Notably, the distribution and frequency of different mRNA variants vary in different populations. However, studies concerning this in Mexico are limited, and the results have been inconclusive. This study therefore aimed to determine the distribution of BCR::ABL1 mRNA variants in different clinical phases of CML and their effect on hematological parameters and patient survival. This study included 33 patients, whose demographic, clinical, and molecular data on BCR::ABL1 mRNA variants and hematological parameters were collected to identify potential associations. A total of 84.8% (n = 28) of patients had BCR::ABL1 translocation and increased platelet and basophil counts. The most frequent mRNA variant was b3a2 (64.3%), followed by b2a2 (28.6%) and e1a2 (3.6%). Concerning the clinical phases of CML, 75.8% (n = 25), 21.2% (n = 7), and 3% (n = 1) of patients were in the chronic, blast, and accelerated phases, respectively. Moreover, the b3a2 mRNA variant was more commonly identified in patients in the chronic phase. No correlation was observed between mRNA variant expression and patient survival. However, b2a2 was indicative of patients with longer survival as well as those treated with imatinib or nilotinib. Additionally, platelet count could be a marker of BCR::ABL1 translocation.

Chronic myeloid leukemia (CML) is associated with the Philadelphia chromosome and distinct BCR::ABL1 gene transcripts. We assessed the frequencies of these transcripts in Mexico, Latin America, and worldwide. We determined the prevalence of BCR::ABL1 transcripts in CML patients and intercontinental or regional variations using specialized databases and keywords. We analyzed 34 studies from 20 countries, encompassing 5795 patients. Keyword-based searches in specialized databases guided data collection. ANOVA was employed for transcript distribution analysis. The b3a2 transcript was most prevalent globally, followed by b2a2 , with e1a2 being the least frequent. Interestingly, Mexico City exhibited a higher incidence of b2a2 , while b3a2 predominated in the remaining country. Overall, no significant intercontinental or regional variations were observed. b3a2 was the most common BCR::ABL1 transcript worldwide, with b2a2 following closely; e1a2 was infrequent. Notably, this trend remained consistent in Mexico. Evaluating transcript frequencies holds clinical relevance for CML management. Understanding the frequency of transcript informs personalized CML treatments.

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Introduction: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region., Objective: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology., Methods: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays., Results: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, and 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples., Conclusions: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs., (Copyright: © 2022 Permanyer.)

Introduction: Transplants and organ donation are greatly aided by future medical professionals having adequate knowledge of this topic. This study aimed to elucidate the level of Mexican medical students' knowledge in the field of transplants and organ donation., Materials and Methods: The evaluation instrument was designed and validated. The design used simple sampling with replacement, selecting a random sample of 5 universities from among the institutional members of the Mexican Association of Departments and Schools of Medicine (Asociación Mexicana de Facultades y Escuelas de Medicina [AMFEM]). The sample was composed of 3214 medical students. Measures of central tendency were determined, and the mean scores obtained across the different universities were compared using a Kruskal-Wallis test. The odds ratio was calculated for the students whose school or department included instruction on transplants and donation within their curriculum. Kendall correlation was used for the students' academic grade level and score. All analyses considered a threshold of P < .05., Results: A questionnaire was administered to a sample of 2563 students to evaluate their knowledge of transplants and organ donation. The average score was 4.02 on a scale of 0 to 10 (standard deviation 0.03), with a 95% confidence interval (3.96-4.08). Students whose school or department taught the subject of transplants and donations within their curriculum obtained an odds ratio of 1.44 (P = .0000822)., Conclusions: The findings of this study suggest that medical students in Mexico do not have sufficient knowledge of transplants and organ donation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This study presents a prediction of putative miRNA within several Human Papillomavirus (HPV) types by using bioinformatics tools and a strategy based on sequence and structure alignment. Currently, little is known about HPV miRNAs., Methods: Computational methods have been widely applied in the identification of novel miRNAs when analyzing genome sequences. Here, ten whole-genome sequences from HPV-6, -11, -16, -18, -31, -33, -35, -45, -52, and -58 were analyzed. Software based on local contiguous structure-sequence features and support vector machine (SVM), as well as additional bioinformatics tools, were utilized for identification and classification of real and pseudo microRNA precursors., Results: An initial analysis predicted 200 putative pre-miRNAs for all the ten HPV genome variants. To derive a smaller set of pre-miRNAs candidates, stringent validation criteria was conducted by applying <‒10 ΔG value (Gibbs Free Energy). Thus, only pre-miRNAs with total scores above the cut-off points of 90% were considered as putative pre-miRNAs. As a result of this strategy, 19 pre-miRNAs were selected (hpv-pre-miRNAs). These novel pre-miRNAs were located in different clusters within HPV genomes and some of them were positioned at splice regions. Additionally, the 19 identified pre-miRNAs sequences varied between HPV genotypes. Interestingly, the newly identified miRNAs, 297, 27b, 500, 501-5, and 509-3-5p, were closely implicated in carcinogenesis participating in cellular longevity, cell cycle, metastasis, apoptosis evasion, tissue invasion and cellular growth pathways., Conclusions: The novel putative miRNAs candidates could be promising biomarkers of HPV infection and furthermore, could be targeted for potential therapeutic interventions in HPV-induced malignancies., (Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.)

Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients' blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials. [ABSTRACT FROM AUTHOR]

The role of human papillomavirus (HPV) infection in penile carcinoma (PeC) is currently reported and about half of the PeC is associated with HPV16 and 18. We used a PCR-based strategy by using HPV general primers to analyze 86 penile carcinomas paraffin-embedded tissues. Some clinical data, the histological subtype, growth pattern, and differentiation degree were also collected. The amplified fragments were then sequenced to confirm the HPV type and for HPV16/18 variants. DNA samples were also subjected to relative real time PCR for hTERC gene copy number. Some clinical data were also collected. Global HPV frequency was 77.9%. Relative contributions was for HPV16 (85%), 31 (4.4%), 11 (4.4%), 58, 33, 18, and 59 (1.4% each one). Sequence analysis of HPV16 identified European variants and Asian-American (AAb-c) variants in 92% and in 8% of the samples, respectively. Furthermore hTERC gene amplification was observed in only 17% of the cases. Our results suggest that some members of HPV A9 group (represented by HPV16, 58, and 31) are the most frequent among PeC patients studied with an important contribution from HPV16 European variant. The hTERC gene amplification could be poorly related to penile epithelial tissue.

Introduction: Non-medical staff members in hospitals are highly credible at population level, and are a source of opinion even though they do not have sufficient medical training., Objectives: To analyse the attitudes of non-medical professionals of Spanish and Latin American hospitals towards organ donation and identify the factors that influence these attitudes., Material and Method: Through the "Proyecto Colaborativo Internacional Donante" (International Collaborative Donor Project), a stratified random sample was selected from non-medical services of eleven hospitals: 3 Spanish (n=277), 5 Mexican (n=632), 2 Cuban (n=42) and 1 Costa Rican (n=101)., Results: Of the 1052 professionals surveyed, 72% (n=754) were in favour of donating an organ after death. By country, 98% of Cubans, 80% of Mexicans, 66% of Costa Ricans and 52% of Spanish were in favour (P<.001). The most influential variables were: 1) country, with results being more positive in Mexico (odds ratio [OR]=2.197), 2) believing in the possibility that they will require a transplant (OR=2.202), 3) having discussed the issue with their family (OR=3.23), 4) the positive attitude of their partner towards donation (OR=3.322), 5) not being concerned about possible mutilation of their body after donation (OR=3.378), 6) preferring options other than burial (OR=2.525), 7) accepting an autopsy (OR=2.958)., Conclusions: The attitude of non-medical staff members of hospitals towards the donation of their own organs varies greatly depending on the country of the respondent. Psychosocial factors that influence these attitudes are similar to those described at the population level.

Background: Human Papillomavirus (HPV) in cervical epithelium has been identified as the main etiological factor in the developing of Cervical Cancer (CC), which has recently become a public health problem in Mexico. This finding has allowed for the development of vaccines that help prevent this infection. In the present study, we aimed to determine the prevalence and HPV type-distribution in Mexican women with CC, high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), and Normal cytology (N) to estimate the impact of the HPV vaccines., Methods: The PubMed database was used to identify and review all articles that reported data on HPV prevalence in CC, precursor lesions, and normal cytology of Mexican women., Results: A total of 8,706 samples of the tissues of Mexican women were stratified according to diagnosis as follows: 499 for CC; 364 for HSIL; 1,425 for LSIL, and 6,418 for N. According to the results, the most prevalent genotypes are the following: HPV16 (63.1%), -18 (8.6%), -58, and -31 (5%) for CC; HPV-16 (28.3%), 58 (12.6%), 18 (7.4%), and 33 (6.5%) for HSIL; HPV-16 (13.1%), 33 (7.4%), 18 (4.2%), and 58 (2.6%) for LSIL, and HPV-16 (3.4%), 33 (2.1%), 18, and 58 (1.2%) for N., Conclusions: Taken together, genotypes 58 and 31 (10%) are more common than type 18 (8.6%) in CC. Therefore, the inclusion of these two genotypes in a second-generation vaccine would provide optimal prevention of CC in Mexico.

Background: Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed., Methods: In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels., Results: Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses)., Conclusion: The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097.

The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex) molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens) molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing.

We developed a procedure to detect the 7 point mutations at Cys634 of the proto-oncogene RET, which is responsible for medullary thyroid carcinoma (MTC). Genomic DNA was prepared from blood samples obtained from normal and MTC-affected individuals belonging to a family with a history of the disease. The RET genotype for each individual was first established by performing restriction and sequencing analyses. Single-stranded target DNA was prepared by asymmetric polymerase chain reaction (PCR) amplification of a 93-bp fragment containing Cys634. The target was annealed with pairs of prelabeled stacking oligonucleotides designed to create appropriate 7-nucleotide gaps, which served as the sites of subsequent hybridization with glass-immobilized 7-mer probes. The target-stacking oligonucleotide duplexes were hybridized with DNA chips containing a set of eight 7-mer probes designed to detect the wild-type sequence and the seven point mutations described. We tested two sets of immobilized probes containing internal or 5'-terminal codon-634 single-base variations. Both groups of probes were able to discriminatively identify the mutations. The hybridization patterns indicated that the disease in this family was due to the C634Y mutation, in accord with the original sequence analysis. The hybridization-based mutation assignment was additionally supported by determination of the control homozygous and heterozygous hybridization patterns produced with synthetic targets having the normal or codon 634 mutant sequences. The effects of mismatch type and nearest-neighbor sequences on the occurrence of false-positive (mismatched) hybridizations are discussed.

Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are characterized by development of medullary thyroid carcinoma (MTC) and caused by germline RET mutations. Patients with MEN 2A also develop pheochromocytoma and/or hyperparathyroidism (HPT). However, MEN 2A-affected individuals could display the FMTC phenotype at first clinical manifestation. To establish the correct phenotype and improve clinical management of patients affected by hereditary MTC, clinical screening, RET mutational analysis, penetrance of MTC, and genotype-phenotype correlation were performed in a large, suspected FMTC kindred of 86 individuals. Germline C634Y RET mutation was confirmed in 22 individuals, 15 of whom were thyroidectomized when high serum calcitonin levels were detected. MTC was confirmed in 12 individuals and C-cell hyperplasia in 3. HPT was detected in two patients. High penetrance of MTC at young age (79% at 30 yr of age) was found. This family was considered to be affected by FMTC for several years because MTC was the sole clinical manifestation. However, our results allowed reclassifying the family as MEN 2A, thereby improving clinical management of family members. Our findings regarding penetrance and genotype-phenotype correlation suggest that patients considered to have FMTC may in fact have MEN 2A in some kindreds.

Objective: Specific hr-HPV genotypes have different natural histories and different oncogenic capacity. This study aimed to investigate the risk of CIN2+ recurrence of the individual genotypes and evaluate how the duration of HPV persistence influences the risk of developing recurrent 16 cervical dysplasia of high grade (CIN2+). Methods: Data from patients with persistent HPV infection after primary conization were retrospectively extracted. Kaplan-Meier proportional hazards models were used to evaluate associations between the duration of HPV persistence and the risk of developing recurrent CIN2+. Kruskal-Wallis testing with Dunn's multiple comparison test was used to test whether there was a statistically significant difference in the time to development of tumor recurrences between different genotypes. Results: Overall, 333 patients met the inclusion criteria. In 285 cases the HPV infection was persistent, in 48 cases (18%) it was transient, i.e., different genotypes after LEEP. Overall were diagnosed 39 relapses (13.7%), 79.5% (31/39 cases) were due to genotype 16, 20.5% (8/39) were linked to the other genotypes. Persistence of genotype 16 showed a 7-fold increased risk of developing a CIN2+ relapse, OR = 7.08 (95%CI: 3.12–16.08). Furthermore, the majority of relapses (38/39) occurred within 24 months of persistence with a cut-off represented by 18 months (p = 0.001) in which the relapse rate is maximum and the most frequently found genotype was the 16th with 31 (79.5%) cases of recurrence. Kruskal-Wallis test with Dunn's multiple comparisons has shown statistically significant difference in the time of development of CIN2 relapses among HPV16 and other genotypes. (p < 0.05). Kaplan-meier analysis has shown statistically significant difference between the time to CIN2+ relapse onset in patients with HPV 16 infection and patients with other hrHPV genotypes. (p < 0.05) Conclusions: the study results suggest that persistent HPV infection after LEEP with the same HR genotype present before surgery represents one of the most important predictive factors of the risk of CIN2+ recurrence. The persistence of HPV16 for the first 18 months strongly correlates with the risk of developing a CIN2+ recurrence. [ABSTRACT FROM AUTHOR]

Penile cancer (PC) is a rare male malignant tumor, with early lymph node metastasis and poor prognosis. Human papillomavirus (HPV) plays a key role in the carcinogenesis of PC. This review aims to summarize the association between HPV infection and PC in terms of virus–host genome integration patterns (the disrupted regions in the HPV and PC genome), genetic alterations, and epigenetic regulation (methylation and microRNA modification) occurring in HPV and PC DNA, as well as tumor immune microenvironment reprogramming. In addition, the potential of HPV vaccination strategies for PC prevention and treatment is discussed. Understanding of the HPV-related multidimensional mechanisms and the application of HPV vaccines will promote rational and novel management of PC. [ABSTRACT FROM AUTHOR]

Brachybacterium conglomeratum, traditionally considered an environmental bacterium, has recently garnered attention for its potential involvement in human health. While prior research hinted at its pathogenic role in humans, our study aims to determine its prevalence and associations in diverse clinical contexts. We examined vaginal swabs from three distinct patient groups: patients with low-grade squamous intraepithelial lesions (LSIL), patients with cervicovaginal infections, and patients with a history of precancerous lesions undergoing follow-up. B. conglomeratum was present in all three patient groups, with the highest prevalence observed in the LSIL group. Statistically significant associations were primarily identified in the LSIL group, where B. conglomeratum was present in 60% of cases. Notably, the LSIL group exhibited coinfections with multiple high-risk oncogenotypes of human papillomavirus (HPV), suggesting potential synergistic effects, and understanding these microbial relationships and their influence on viral persistence, particularly with HPV, holds promise for mitigating HPV-related carcinogenesis. Furthermore, Gardnerella vaginalis and Atopobium vaginae were frequently detected in this group, along with Ureaplasma parvum as the predominant sexually transmitted bacterium. In all cases, B. conglomeratum was found in association with these microorganisms rather than as a sole pathogen. This coexistence underscores the intricate microbial interactions within cervicovaginal infections and precancerous lesions. This study marks the first report of B. conglomeratum prevalence in women with these clinical conditions. [ABSTRACT FROM AUTHOR]

Somatic copy number alterations (SCNA) involving either a whole chromosome or just one of the arms, or even smaller parts, have been described in about 88% of human tumors. This study investigated the SCNA profile in 40 well-characterized sporadic medullary thyroid carcinomas by comparative genomic hybridization array. We found that 26/40 (65%) cases had at least one SCNA. The prevalence of SCNA, and in particular of chromosome 3 and 10, was significantly higher in cases with a RET somatic mutation. Similarly, SCNA of chromosomes 3, 9, 10 and 16 were more frequent in cases with a worse outcome and an advanced disease. By the pathway enrichment analysis, we found a mutually exclusive distribution of biological pathways in metastatic, biochemically persistent and cured patients. In particular, we found gain of regions involved in the intracellular signaling and loss of regions involved in DNA repair and TP53 pathways in the group of metastatic patients. Gain of regions involved in the cell cycle and senescence were observed in patients with biochemical disease. Finally, gain of regions associated with the immune system and loss of regions involved in the apoptosis pathway were observed in cured patients suggesting a role of specific SCNA and corresponding altered pathways in the outcome of sporadic MTC. [ABSTRACT FROM AUTHOR]

Allorecognition is known to involve a large number of lymphocytes carrying diverse T-cell receptor repertoire. Thus, one way to understand allorecognition and rejection mechanisms is via high-throughput sequencing of T-cell receptors. In this study, in order to explore and systematize the properties of the alloreactive T-cell receptor repertoire, we modeled direct and indirect allorecognition pathways using material from inbred mice in vitro and in vivo. Decoding of the obtained T-cell receptor genes using high-throughput sequencing revealed some features of the alloreactive repertoires. Thus, alloreactive T-cell receptor repertoires were characterized by specific V-gene usage patterns, changes in CDR3 loop length, and some amino acid occurrence probabilities in the CDR3 loop. Particularly pronounced changes were observed for directly alloreactive clonotypes. We also revealed a clustering of directly and indirectly alloreactive clonotypes by their ability to bind a single antigen; amino acid patterns of the CDR3 loop of alloreactive clonotypes; and the presence in alloreactive repertoires of clonotypes also associated with infectious, autoimmune, and tumor diseases. The obtained results were determined by the modeling of the simplified allorecognition reaction in inbred mice in which stimulation was performed with a single MHCII molecule. We suppose that the decomposition of the diverse alloreactive TCR repertoire observed in humans with transplants into such simple reactions will help to find alloreactive repertoire features; e.g., a dominant clonotype or V-gene usage pattern, which may be targeted to correct the entire rejection reaction in patients. In this work, we propose several technical ways for such decomposition analysis, including separate modeling of the indirect alloreaction pathway and clustering of alloreactive clonotypes according to their ability to bind a single antigen, among others. [ABSTRACT FROM AUTHOR]

The present study was conducted on the MHC class I (BoLA-A/BuLA-A) gene in Sahiwal, Jersey, Hariana, and Tharparkar breeds of cattle and Murrah, Mehsana, and Bhadawari breeds of buffalo to study the polymorphism. Exons 7–8 of the MHC class I gene was first characterized for polymorphism study in buffalo and the results reveal that this gene has a higher level of nucleotide changes than the cattle. Genes were investigated for polymorphisms in 285 animals of cattle and buffalo breeds. Molecular characterization of the MHC class I (BoLa-A/Bula-A) gene reveals a higher degree of polymorphism at the nucleotide level in cattle and buffalo. Results revealed this region has a higher level of polymorphisms in buffalo as campared to the cattle. Alul restriction patterns were monomorphic except for three different patterns but it was able to illustrate the differences in buffalo and cattle. SSCP analysis of exons 7–8 showed remarkable differences in cattle and buffalo. Sequence analysis revealed more closeness of Murrah breed with crossbred and indigenous cattle than Holstein Friesian. Exon 8 had more deletion and stop codon as compared to exon 7. The investigation confirmed that MHC class I BoLa-A/Bula-A exons 7–8 is highly polymorphic in buffalo as compared to cattle. [ABSTRACT FROM AUTHOR]

Identification of CD8+ T cell epitopes is critical for the development of immunotherapeutics. Existing methods for major histocompatibility complex class I (MHC class I) ligand discovery are time intensive, specialized and unable to interrogate specific proteins on a large scale. Here, we present EpiScan, which uses surface MHC class I levels as a readout for whether a genetically encoded peptide is an MHC class I ligand. Predetermined starting pools composed of >100,000 peptides can be designed using oligonucleotide synthesis, permitting large-scale MHC class I screening. We exploit this programmability of EpiScan to uncover an unappreciated role for cysteine that increases the number of predicted ligands by 9–21%, reveal affinity hierarchies by analysis of biased anchor peptide libraries and screen viral proteomes for MHC class I ligands. Using these data, we generate and iteratively refine peptide binding predictions to create EpiScan Predictor. EpiScan Predictor performs comparably to other state-of-the-art MHC class I peptide binding prediction algorithms without suffering from underrepresentation of cysteine-containing peptides. Thus, targeted immunopeptidomics using EpiScan will accelerate CD8+ T cell epitope discovery toward the goal of individual-specific immunotherapeutics. Peptides that bind MHC class I are readily identified with a programmable, high-throughput method. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has shown promise clinically, but resistance to therapies remains an issue. Using novel combinations of immunotherapies may help overcome these barriers. Here, we tested combinations of immunotherapy agents that were administered intratumorally using a mouse model of lymphoma. We show that combination treatment with multiple immune-modulating agents allowed for greater tumor control and induced tumor-specific long-term immunological memory that was T cell dependent. Combination treated animals showed modest alterations in immune cell subsets in lymphoid tissues and had increased immune infiltration to tumors 24 h after treatment. Future studies should evaluate the impact of other immunotherapy combinations on a variety of tumor types. The use of immunotherapies has shown promise against selective human cancers. Identifying novel combinations of innate and adaptive immune cell-activating agents that can work synergistically to suppress tumor growth and provide additional protection against resistance or recurrence is critical. The A20 murine lymphoma model was used to evaluate the effect of various combination immunotherapies administered intratumorally. We show that single-modality treatment with Poly(I:C) or GM-CSF-secreting allogeneic cells only modestly controls tumor growth, whereas when given together there is an improved benefit, with 50% of animals clearing tumors and surviving long-term. Neither heat nor irradiation of GM-CSF-secreting cells enhanced the response over use of live cells. The use of a TIM-3 inhibitory antibody and an OX40 agonist in combination with Poly(I:C) allowed for improved tumor control, with 90% of animals clearing tumors with or without a combination of GM-CSF-secreting cells. Across all treatment groups, mice rejecting their primary A20 tumors were immune to subsequent challenge with A20, and this longstanding immunity was T-cell dependent. The results herein support the use of combinations of innate and adaptive immune activating agents for immunotherapy against lymphoma and should be investigated in other cancer types. [ABSTRACT FROM AUTHOR]

Major Histocompatibility Complex (MHC) molecules have been proposed to play a role in Sickle Cell Disease (SCD) pathophysiology. Endothelial cells express MHC molecules following exposure to cytokines. SCD is characterized, in part, by vascular endothelial cell activation, increased oxidative stress, sickle cell adhesion, and excess levels of endothelin-1 (ET-1) contributing to vaso occlusive crises. ET-1 activates endothelial cells, induces oxidative stress and inflammation, and alters erythrocyte volume homeostasis. However, the role of ET-1 on MHC regulation in SCD is unclear. We first studied two sickle transgenic knockout mouse models of moderate to severe disease phenotype, bS-Antilles and Berkeley (BERK) mice. We observed significant increases in H2-Aa mRNA levels in spleens, lungs, and kidneys from transgenic sickle mice when compared to transgenic knockout mice expressing human hemoglobin A (HbA). Mice treated for 14 days with ET-1 receptor antagonists significantly reduced H2-Aa mRNA levels. We characterized the effect of ET-1 on MHC class II expression in the human endothelial cell line EA.hy926. We observed dose-dependent increases in the expression of MHC class II (HLA-DRA) and MHC transcription factor (CIITA) that were significantly blocked by treatment with BQ788, a selective blocker of ET-1 type B receptors. Chromatin immunoprecipitation studies in EA.hy926 cells showed that ET-1 increased Histone H3 acetylation of the HLA-DRA promoter, an event blocked by BQ788 treatment. These results implicate ET-1 as a novel regulator of MHC class II molecules and suggest that ET-1 receptor blockade represents a promising therapeutic approach to regulate both immune and vascular responses in SCD. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) genotypes differ by geographic location. With the advent of HPV vaccination and HPV-based cervical screening tests in Ethiopia, a nationwide dataset on the genotype distribution of HPV among women has paramount importance in the fight against cervical cancer. However, there is limited data in this regard in the northwest part of the country. Therefore, this study aimed to identify the genotype distribution of high-risk HPVs among women presenting with cervical abnormalities. Methods: A health facility-based cross-sectional study was conducted at Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar–Ethiopia. Women aged ≥ 30 years who visited the hospital gynecology unit from 01 March 2019 to 30 October 2021 were included. Following general and pelvic examinations, a senior gynecologist collected cervical punch biopsies for histopathological examinations and cervical swabs for HR-HPV detection using the Abbott Alinity m system (Abbott Molecular, Des Plaines, IL, USA). Extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay (INNO-LiPA; Fujirebio Europe, Ghent, Belgium) as per the manufacturer protocols at the Institute of Virology, Leipzig University Hospital, Germany. Results: We included 355 women with a mean age of 46.4 ± 11.4 years. The majority of the participants, 277 (79.4%) were sexually active before the age of 18 years and 180 (51.6%) had multiple sexual partners. Forty-eight (13.5%) of the participants were HIV positive. The proportion of HR-HPV was 53.0% (n = 188; 95%CI: 47.8–58.1%). From these samples, 13 different HR-HPV types with a total of 258 sequences were identified. The detection of HR-HPV increased significantly with an increase in the age of the participants. The predominant identified HR-HPV was HPV16, 50.4% followed by HPV31 (9.7%), HPV33 (8.5%), HPV39, and HPV68 each (5.8%) and HPV18 (4.7%). Of the total HR-HPV-positive women, 23.9% (45/188) were infected with multiple HR-HPV types. All HPV16, HPV18, HPV35, and HPV45 genotypes (as a single or in coinfections) were found to be associated with either high-grade lesions or cervical cancer. Conclusions: HR-HPV infection was reportedly higher among women in the present study area. Based on our findings, we strongly recommend the nonavalent HPV vaccine for immunization and any HPV-based screening method to take into consideration the predominant genotypes circulating in the country. The role of multiple HPV infections in high-grade cervical lesions entails further study in Ethiopia. [ABSTRACT FROM AUTHOR]

Background: Solid organ transplantation is a life-saving medical operation that has progressed greatly because of developments in diagnostic tools and histocompatibility tests. Crossmatching for complement-dependent cytotoxicity (CDC) and human leukocyte antigen (HLA) typing are two important methods for checking graft compatibility and reducing the risk of graft rejection. HLA typing and CDC crossmatching are critical in kidney, heart, lung, liver, pancreas, intestine, and multi-organ transplantation., Methods: A systematic literature search was conducted on the internet, using PubMed, Scopus, and Google Scholar databases, to identify peer-reviewed publications about solid organ transplants, HLA typing, and CDC crossmatching., Conclusion: Recent advances in HLA typing have allowed for high-resolution evaluation, epitope matching, and personalized therapy methods. Genomic profiling, next-generation sequencing, and artificial intelligence have improved HLA typing precision, resulting in better patient outcomes. Artificial intelligence (AI) driven virtual crossmatching and predictive algorithms have eliminated the requirement for physical crossmatching in the context of CDC crossmatching, boosting organ allocation and transplant efficiency. This review elaborates on the importance of HLA typing and CDC crossmatching in solid organ transplantation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The recent advances of quantum biology suggest a potential role in biomedical research. Studies related to electromagnetic fields, proton pumping in mitochondrial respiratory chain, quantum theory of T-cell receptor (TCR)-degeneracy, theories on biophotons, pyrophosphates or tubulin as possible carriers for neural information, and quantum properties of ions and protons, might be useful for understanding mechanisms of some serious immune, cardiovascular, and neural pathologies for which classic biomedical research, based on biochemical approach, is struggling to find new therapeutic strategies. A breakthrough in medical knowledge is therefore needed in order to improve the understanding of the complex interactions among various systems and organs typical of such pathologies. In particular, problems related to immune system over-activation, to the role of autonomic nervous system (ANS) dysfunction in the obstructive sleep apnea (OSA) syndrome, to the clinical consequences of ion channels dysfunction and inherited cardiac diseases, could benefit from the new perspective provided by quantum biology advancement. Overall, quantum biology might provide a promising biophysical theoretic system, on which to base pathophysiology understanding and hopefully therapeutic strategies. With the present work, authors hope to open a constructive and multidisciplinary debate on this important topic. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the epidemiological, diagnostic and therapeutic data of hematological malignancies in pregnancy. Leukemia in pregnancy is rare, and literature data are not extensive. Risk factors, epidemiology and pathogenesis of these diseases are not fully developed. Furthermore, there is a detailed report on the complications in pregnancy and the overall (per trimester) management of these diseases, specifically their treatment strategy. The possibility of achieving a future pregnancy in women with leukemia is described in the present study. The limited clinical research data currently available is mainly due to the inability to conduct randomized clinical trials for ethical reasons. Further research is needed, firstly due to the importance of these diseases for the pregnant woman and the fetus, and secondly, due to the continuous development of novel anticancer drugs that aim to improve the prognosis of these diseases. [ABSTRACT FROM AUTHOR]

HLA molecules are expressed in almost all nucleated cells of the body. These molecules are extremely variable and responsible for tissue specificity recognition. Precise HLA typing is crucial for tissue and organ transplantation. Usually, HLA‐typing NGS methods are based on the assignment of reads to a certain previously reported HLA allele presented in the IPD‐IMGT/HLA Database. But there is a limited number of tools able to identify novel alleles that have not yet been reported and thus absent in the database. Such alleles carry mismatches distinguishing them from all known alleles in the database. Therefore, manual evaluation of the identified HLA alleles in the genome browser is a compulsory step in the analysis, and one that is labor intensive and time consuming. We present the development and validation of a freely available web‐application for the identification of novel HLA alleles in the most relevant HLA class I and II genes from NGS data. The tool can also be used for automated data quality assessment. The software was validated by analyzing 330 alleles. The results are concordant with orthogonal methods. [ABSTRACT FROM AUTHOR]

Background: Amnion-derived mesenchymal stem cells (AM-MSCs) are an attractive source of stem cell therapy for patients with irreversible liver disease. However, there are obstacles to their use due to low efficiency and xeno-contamination for hepatic differentiation. Methods: We established an efficient protocol for differentiating AM-MSCs into hepatic progenitor cells (HPCs) by analyzing transcriptome-sequencing data. Furthermore, to generate the xeno-free conditioned differentiation protocol, we replaced fetal bovine serum (FBS) with polyvinyl alcohol (PVA). We investigated the hepatocyte functions with the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4. Finally, to test the transplantable potential of HPCs, we transferred AM-MSCs along with hepatic progenitors after differentiated days 11, 12, and 13 based on the expression of hepatocyte-related genes and mitochondrial function. Further, we established a mouse model of acute liver failure using a thioacetamide (TAA) and cyclophosphamide monohydrate (CTX) and transplanted AM-HPCs in the mouse model through splenic injection. Results: We analyzed gene expression from RNA sequencing data in AM-MSCs and detected downregulation of hepatic development-associated genes including GATA6, KIT, AFP, c-MET, FGF2, EGF, and c-JUN, and upregulation of GSK3. Based on this result, we established an efficient hepatic differentiation protocol using the GSK3 inhibitor, CHIR99021. Replacing FBS with PVA resulted in improved differentiation ability, such as upregulation of hepatic maturation markers. The differentiated hepatocyte-like cells (HLCs) not only synthesized and secreted albumin, but also metabolized drugs by the CYP3A4 enzyme. The best time for translation of AM-HPCs was 12 days from the start of differentiation. When the AM-HPCs were transplanted into the liver failure mouse model, they settled in the damaged livers and differentiated into hepatocytes. Conclusion: This study offers an efficient and xeno-free conditioned hepatic differentiation protocol and shows that AM-HPCs could be used as transplantable therapeutic materials. Thus, we suggest that AM-MSC-derived HPCs are promising cells for treating liver disease. [ABSTRACT FROM AUTHOR]

Infections caused by the human immunodeficiency virus (HIV) and human papillomavirus (HPV) cause thousands of deaths worldwide each year. So far, there has been no consensus on whether there is a direct relationship between the incidence of neoplasms and the immunosuppression caused by HIV that could help understand if coinfection increases the likelihood of cervical cancer. The objective of the study was to identify the presence of genetic variants of HPV in a group of HIV-positive women and their possible association with cervical cancer. Cervical samples were taken from HIV-positive patients for cytological analysis to identify the HPV genotype by polymerase chain reaction (PCR) and sequencing. The most prevalent L1 capsid protein mutations in the HPV genotype were analyzed in silico. Various types of HPV were identified, both high-risk (HR) and low-risk (LR). The most prevalent genotype was HPV51. Analysis of the L1 gene sequences of HPV51 isolates showed nucleotide variations. Of the samples analyzed in Puebla, Mexico, HPV51 had the highest incidence (17.5%, 7/40). Different mutations, which could be used as population markers, were detected in this area, and they have not been reported in the L1 databases for HPV51 in Mexico. Genotypes 6, 14, 86, 87, 89, and 91, not detected or reported in samples from patients with HPV in Mexico, were also identified. Data from the population analyzed suggest no direct relationship between HIV immunosuppression and cervical cancer, regardless of the high- or low-risk HPV genotype. Furthermore, it is possible to develop regional population markers for the detection of HPV based on the mutations that occur in the sequence of nucleotides analyzed. [ABSTRACT FROM AUTHOR]

Summary: Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell‐mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi‐parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post‐transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+CD154+ and CD8+CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient–donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con‐A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+CD154+ T cells (P = 0·001) and a low percentage of CD8+CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut‐off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+CD154+ (P = 0·001) and CD8+CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+CD154+, CD8+CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post‐transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+CD154+ and CD8+CD154+ T cells in parallel with other transplant factors. [ABSTRACT FROM AUTHOR]

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Human papillomavirus genotype 16 (HPV16) is the most frequent high-risk HPV (HR-HPV) identified in cervical precursor lesions and cervical cancer (CC) worldwide. The oncogenic potential of HPV16 is partly dependent on the lineage involved in the infection and the presence of clinically relevant mutations. In this report, we present the distribution of HR-HPV and the mutational profile and intra-host variability of HPV16 lineages, based on analysis of the long control region (LCR) and the E6 gene in samples with normal cytology (n = 39), squamous intraepithelial lesions (n = 25), and CC (n = 39). HR-HPV genotyping was performed using multiplex real-time PCR. HPV16 lineage assignments and mutation frequencies were determined by conventional PCR and Sanger DNA sequencing, and intra-patient viral populations were analyzed using next-generation sequencing (NGS). The most frequent HR-HPV type was HPV16, followed by HPV31 and HPV18. The frequency of HPV16 sublineages was A1/A2 > D2 > D3 and B1. Moreover, the most frequent mutations, both in samples from this study and in the available sequences from Mexican isolates in the GenBank database were LCR-G7518A, which is involved in carcinogenesis, and E6-T350G (producing L83V), associated with persistence of infection. Otherwise, deep sequencing revealed high conservation of viral lineages and mutations, independently of the stages studied. In conclusion, the high frequency and stability of these molecular markers, as well as the circulating viral lineages, could be related to the incidence of CC associated with HPV16. Hence, they deserve a broader analysis to determine the risk of specific populations for progression of the disease. [ABSTRACT FROM AUTHOR]

Lung transplantation is increasingly practiced for patients with end-stage lung disease. The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies, mainly directed against the protein products of the HLA complex of the organ donor. While the association between antibody mediated rejection and allograft damage has been well established in renal and heart transplantation, it has not yet been well characterized in lung transplantation. This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class I and II antigens. The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or de novo post-transplant circulating antibodies. Finally, potential mechanisms, which may act individually or in combination, of antibody mediated damage to solid organ transplants are considered. [ABSTRACT FROM AUTHOR]

Human papillomavirus has been identified as a main etiological agent in the development of cervical cancer. HPV 16 and 18 have been reported the most widely prevalent genotypes worldwide. We conducted a study analyzing the prevalence of high and low risk human papillomavirus viral types in the Mexican state of Aguascalientes and neighboring cities in the states of Jalisco and Zacatecas in central Mexico. Specific viral genotype was determined by a PCR and hybridization-based detection test. The presence of 37 high- and low-risk HPV genotypes was evaluated in 883 female participants. Of these, 350 presented low-grade squamous intraepithelial lesions (LGSIL), 176 presented high-grade squamous intraepithelial lesions (HGSIL), 107 suffered from cervical cancer and 250 women with negative cytological report for intraepithelial lesion or malignancy (NILM). HPV 51 was the most prevalent genotype, followed by HPV 16: overall prevalence of HPV 51, including single infections and co-infections was 31.2% in women with LGSIL, whereas prevalence of HPV 16 was 25.1%. Among women with HGSIL, HPV 51 prevalence was 47.2% and HPV 16 was 30.1%. Prevalence of HPV 51 in women with cervical cancer was 49.5% and type 16 was 33.6%. Between single and co-infections, most co-infections were not associated with later stages of the disease, except 51/16 and some others. HPV 51 showed a significant correlation with the progression of the disease (OR = 10.81 for LGSIL, 19.38 for HGSIL and 22.95 for ICC), and when analyzing all other genotypes, five different groups depending on their correlation with all lesion grades were determined. According to our findings, HPV genotype 51 has a higher prevalence than HPV 16 and 18 in the Mexican state of Aguascalientes and neighboring cities in the states of Jalisco and Zacatecas in Central Mexico. [ABSTRACT FROM AUTHOR]

Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease. [ABSTRACT FROM AUTHOR]

Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions. In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol (CBD) can influence their expression profile, improving the therapeutic potential of this cell culture. Following CBD treatment (5μM) for 24 h, gene expression analysis through Next Generation Sequencing (NGS) has revealed several genes differentially expressed between CBD-treated hGMSCs (CBD-hGMSCs) and control cells (CTR-hGMSCs) that were linked to inflammation and apoptosis. In particular, we have demonstrated that CBD treatment in hGMSCs prevented the activation of the NALP3-inflammasome pathway by suppressing the levels of NALP3, CASP1, and IL18, and in parallel, inhibited apoptosis, as demonstrated by the suppression of Bax. CBD treatment was also able to modulate the expression of the well-known mesenchymal stem cell markers (CD13, CD29, CD73, CD44, CD90, and CD166), and other surface antigens. Specifically, CBD led to the downregulation of genes codifying for antigens involved in the activation of the immune system (CD109, CD151, CD40, CD46, CD59, CD68, CD81, CD82, CD99), while it led to the upregulation of those implicated in the inhibition of the immune responses (CD47, CD55, CD276). In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Introduction:Identification of allograft injury, including acute clinical and subclinical injury, is vital in increasing the longevity of the transplanted organ. Acute rejection, which occurs as a result of a variety of immune and non-immune factors including the infiltration of immune cells and antibodies to the donor specific epitopes, poses a significant risk to the organ. Recent years have marked an increase in the discovery of new genomic, transcriptomic, and proteomic biomarkers in molecular diagnostics, which offer better potential for personalized management of the transplanted organ by providing earlier detection of rejection episodes. Areascovered:This review was compiled from key word searches of full-text publications relevant to the field. Expertcommentary:Many of the recent advancements in the molecular diagnostics of allograft injury show much promise, but before they can be fully realized further validation in larger sample sets must be conducted. Additionally, for better informed therapeutic decisions, more work must be completed to differentiate between different causes of injury. Moreover, the diagnostics field is looking at methodologies that allow for multiplexing, the ability to identify multiple targets simultaneously, in order to provide more robust biomarkers and better understanding. [ABSTRACT FROM PUBLISHER]

Human embryonic stem cells (hESCs) are thought to be a promising resource for cell therapy, while it has to face the major problem of graft immunological rejection. Major histocompatibility complex (MHC) class I expressed on the cell surface is the major cause of graft rejection. Transporter associated with antigen presentation 1 (TAP1) and TAP-associated glycoprotein (TAPBP) play important roles in regulating MHC class I expression. In this study, we generated TAP1- and TAPBP-deficient hESC lines, respectively, using transcription activator-like effector nucleases technique. These cells showed deficient expression of MHC class I on the cell surface and reduced immunogenicity compared with wild types, but maintained normal pluripotency, karyotypes, and differentiation ability. Thus, our findings are instrumental in developing a universal cell resource with both pluripotency and hypo-immunogenicity for transplantation therapy in the future. Expression level of MHC class I was markedly reduced in either TAP1(A)- or TAPBP(B)-deficient cell lines. [ABSTRACT FROM PUBLISHER]