Introduction: Turner syndrome is a rare genetic disorder characterised by the presence of one X chromosome and the absence of part or all of an X or Y chromosome and patients may experience delayed puberty and inferti...Introduction: Turner syndrome is a rare genetic disorder characterised by the presence of one X chromosome and the absence of part or all of an X or Y chromosome and patients may experience delayed puberty and infertility. Our study aimed to evaluate the diagnostic delay in our practice and analyze the impact of this diagnostic delay on the effectiveness of patient management. Patients and Methods: Turner syndrome patients were identified from the endocrinology-diabetology nutrition department Database We examined the records of patients in whom the karyotype analysis favoured Turner syndrome. Results: We have selected 5 patients’ records of female patients with Turner syndrome. The mean age was 25, ranging from 19 to 29 years. Primary amenorrhea and characteristic dysmorphic features were observed in all patients. One married patient, who sought consultation for infertility, expressed a desire for pregnancy. Short stature was identified in 3 patients. Primary hypothyroidism and hypertension were respectively found in 1 and 2 patients. Gonadal dysgenesis was noted in 100% of cases. Karyotype analysis revealed monosomy X in 2 patients and mosaic patterns in others. All patients received estrogen-progestin treatment. Antihypertensive therapy was initiated for 2 patients. One patient is on L-thyroxine. In the short term, treatment led to the onset of menstruation after the initial months. Evaluation of treatment efficacy on internal genital organs is yet to be performed. Due to uncertain benefits at this age, growth hormone therapy was not considered for our patients. We provided counseling on assisted reproductive options for couples desiring to conceive. In our study, all patients were placed on estrogen-progestin therapy, and the response appeared favorable. Conclusion: In our practice, the diagnosis of Turner syndrome occurs very late in adulthood, at an age when growth hormone treatment is nearly ineffective. Treatment typically revolves around estrogen-progestin therapy, along with managing other comorbidities such as hypertension and primary hypothyroidism.展开更多
Stem cell therapy holds great promise for the regeneration and repair of damaged tissues and organs.Stem cell therapy has been successfully applied to treat diseases that cannot be cured with conventional medicine.A c...Stem cell therapy holds great promise for the regeneration and repair of damaged tissues and organs.Stem cell therapy has been successfully applied to treat diseases that cannot be cured with conventional medicine.A careful evaluation of the outcomes is required for successful implementation of stem cell therapy.Recently,artificial intelligence(AI)has opened new avenues for research in the stem cell therapy field.The integration of AI can assist in evaluating the quality,efficiency and safety of stem cells by analyzing available data.It has the potential to improve and accelerate progress in various aspects of stem cell research and therapeutic applications.AI is still in its infancy and has certain limitations,such as algorithm validation problems,inadequate data availability,poor data quality,and ethical considerations.Considering the potential of AI to improve stem cell research and therapeutics,this review aims to explore applications of AI in understanding stem cell behavior,identification and characterization,optimization of the delivery methods,stem cell modeling and prediction of mortality risk.In addition,this review highlights the role of AI,machine learning,deep learning,and other subtypes in advancing stem cell biology research.This review also discusses the current limitations,ethical considerations,and future prospective of use of AI in stem cell research and therapeutic applications.展开更多
Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection ...Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection challenging,they are linked to problems.Diagnostic methods like imaging and tissue biopsy are only effective when the tumor has reached a size that can be identified.The liquid biopsy technique,the least intrusive and most convenient diagnostic method,is the subject of this review.It focuses on the significance of single cell analysis in examining uncommon cancer types.The many biomarkers found in bodily fluids and the cancer types they are linked to in children have been assessed,as has the potential route towards early detection and cancer recurrence forecasting.Combining the single cell liquid biopsy with the newest technologies,such as computational and multi-omics approaches,which have improved the efficiency of processing massive and unique genetic data,appears promising.This article discusses on a number of case reports for uncommon pediatric malignancies,such as Neuroblastoma,Medulloblastoma,Wilms Tumor,Rhabdomyosarcoma,Ewing Sarcoma,and Retinoblastoma,as well as their liquid biopsy profiles.Furthermore,the findings raise ethical questions regarding the therapeutic application of the technology as well as possible difficulties related to clinical translation.The likelihood that this single cell liquid biopsy will be clinically validated and eventually used as a routine diagnostic tool for uncommon pediatric cancers will rise with the realistic approach to sensitivity monitoring,specificity upgrading,and optimization.展开更多
Aesthetic medicine is a branch of medicine dedicated to improve an individual’s appearance and overall visual appeal.Conventional aesthetic treatments have limitations,including the risk of complications,allergic rea...Aesthetic medicine is a branch of medicine dedicated to improve an individual’s appearance and overall visual appeal.Conventional aesthetic treatments have limitations,including the risk of complications,allergic reactions,and temporary benefits.Adipose tissue offers a promising alternative to conventional aesthetic treatments.The regenerative properties,accessibility and versatility of adipose tissue make it an attractive option for individuals seeking natural and long-lasting aesthetic results.Adipose tissue is rich source of adipose tissue derived stem cells(ASCs),growth factors and extracellular matrix.It can restore and rejuvenate the damaged and aged tissues.Adipose tissue can be used in different formats such as pure adipose tissue grafts,stromal vascular fraction,nanofat,macrofat,microfat and as a pure population of ASCs.In addition,ASC derived exosomes offer a unique cell-free therapy advantages bioactive molecules like growth factors,cytokines,and microRNAs to stimulate collagen production,improve skin texture,and address pigmentation issues.This review highlights the multifaceted potential of adipose tissue in aesthetic medicine.It discusses its diverse applications,the biological mechanisms involved,and emerging therapeutic approaches.Moreover,this review also highlights the challenges and future direction of using adipose tissue-based therapies for aesthetic treatments.展开更多
Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,pro...Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,prostate,pancreatic,esophageal adenocarcinoma,colorectal carcinoma,renal adenocarcinoma,and pre-and post-menopausal breast cancer.Obesity-induced cellular changes,such as impaired CD8^(+)T cell function,dyslipi-demia,hypercholesterolemia,insulin resistance,mild hyperglycemia,and fluctuating levels of leptin,resistin,adiponectin,and IL-6,contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes.Adipocytes release leptin,a pro-inflammatory substance that stimulates cancer cell proliferation,inflammation,and invasion,altering the tumor cell metabolic pathway.Adiponectin,an insulin-sensitizing adipokine,is typically downregulated in obese individuals.It has antipro-liferative,proapoptotic,and antiangiogenic properties,making it a potential cancer treatment.This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer,draw-ing on an extensive,though non-systematic,survey of the recent literature.This approach allows us to integrate and synthesize findings from various studies,offering a cohesive perspective on emerging themes and potential therapeutic targets.The review explores the metabolic disturbances,cellular alterations,inflammatory responses,and shifts in the tumor microenvironment that contribute to the obesity-cancer link.Finally,it discusses poten-tial therapeutic strategies aimed at disrupting these connections,offering valuable insights into future research directions and the development of targeted interventions.展开更多
OBJECTIVE： Anti-asthma herbal medicine intervention （ASHMITM）, a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic as...OBJECTIVE： Anti-asthma herbal medicine intervention （ASHMITM）, a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy. METHODS： Effects of ASHMI and its components aqueous extracts of Lingzhi （Ganoderma lucidum）, Kushen （Sophora flavescens） and Gancao （Glycyrrhiza uralensis）, on Th2 cytokine secretion by murine memory Th2 cells （D10.G4.1） and eotaxin-1 secretion by human lung fibroblast （HLF-1） cells were determined by measuring levels in culture supernatants by enzyme- linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS： Individual Lingzhi, Kushen and Gancao extracts and ASHMI （the combination of individual extracts） inhibited production of interleukin （IL）-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration （IC2s） values （mg/mL） forASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50values （mg/mL） for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-l. The interaction indices at IC^0 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC^0 values. All interaction indices were below 1 which indicated synergy. CONCLUSION： By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.展开更多
Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected t...Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected to be affected by 2045.Devastating macrovascular consequences(cerebrovascular disease,cardiovascular disease,and peripheral vascular disease)and microvascular complications(like retinopathy,nephropathy,and neuropathy)increase mortality,blindness,kidney failure,and overall quality of life in individuals with diabetes.Clinical risk factors and glycemic management alone cannot predict the development of vascular problems;multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications.In the twenty-first century,technological advancements(genome-wide association studies,nextgeneration sequencing,and exome-sequencing)have led to the identification of genetic variants associated with diabetes,however,these variants can only explain a small proportion of the total heritability of the condition.In this review,we address some of the likely explanations for this"missing heritability",for diabetes such as the significance of uncommon variants,gene-environment interactions,and epigenetics.Current discoveries clinical value,management of diabetes,and future research directions are also discussed.展开更多
Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Medical Genetics(WJMG)as a new member of the World series journal family!Fo...Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Medical Genetics(WJMG)as a new member of the World series journal family!Following the completion of the Human Genome Project,medical genetic research has seen spectacular progress over the last decade.The number of genes that have been linked to Mendelian human traits has grown exponentially and currently this process is peaking with the access to robust genome-wide sequencing power.The genomics revolution is also seen for elucidation of rare and common DNA variants that increase risk for common disorders.Given this fast progress,there is an increasing need for making the results of genetics and genomics studies rapidly and freely available to the larger community.Thus,the decision for inaugurating this new journal is a timely one.The WJMG is a peer-reviewed,open-access periodical centered in all aspects of medical genetics research,with multidisciplinary coverage:from human phenotype to genetic and genomic mutations and variations to the study of pathological mechanisms.If you want to share new results of your research with a link to medical genetics with your peers,you will find the WJMG a good media to publish your papers!展开更多
Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyo...Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies.Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic patients.These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment.While a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant challenge.Point-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex scenarios.Although conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological aspects.Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional therapies.This article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.展开更多
Characterization of an aqueous extract of human placenta, used as a licensed drug for wound healing, leads to the identification of several bioactive components including polydeoxyribonu-cleotides (PDRNs). PDRNs are m...Characterization of an aqueous extract of human placenta, used as a licensed drug for wound healing, leads to the identification of several bioactive components including polydeoxyribonu-cleotides (PDRNs). PDRNs are mixture of DNA fragments of different molecular weight. A spectro-fluorimetric method of quantitation of PDRNs in the aqueous extract of human placenta by using ethidium bromide (EtBr) has been described here. It has been demonstrated by thin layer chromatography (TLC) followed by reversed phase HPLC that EtBr binds specifically with the PDRN fraction of the multi-component extract. The binding specificity of EtBr has been verified by the analysis of emission spectra of the extract. A concentration of 0.29 μg/ml EtBr exhibits a linear range of standard CT-DNA from 0.5 - 5 μg/ml of buffer (R2 = 0.992). The same concentration of EtBr shows a linear range of measurements of placenta extract from 5 - 35 μl/ml of buffer (R2 = 0.976). The points of the curve were the average of three sets where maximum variation observed was ±3%. PDRN content of the extract has been estimated based on the resultant fluorescence emission (after background correction) with respect to the standard calibration curve of calf thymus DNA (CT-DNA). Estimation of PDRN in a large number of batches of placenta extract (n = 100) has been done. The statistical analysis of the estimation was found to be significant and the lower and upper levels of PDRN were 158.30 and 239.03 μg/ml of the extract respectively. This easy-to-use method of estimation of PDRN in multi-component biological extract is reported for the first time. This will help in quantitation of PDRNs for other biological extracts.展开更多
Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga(L.)Lam(a synonym of Visnaga daucoides Gaertn.)plant,which is used to cure various ailments.Many investigations into the bioactive...Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga(L.)Lam(a synonym of Visnaga daucoides Gaertn.)plant,which is used to cure various ailments.Many investigations into the bioactive properties of visnagin have been studied to date.The literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal diseases.Moreover,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates apoptosis.Thus,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical needs.The current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of action.The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.展开更多
Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese exp...Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.展开更多
TToo tthhee eeddiittoorr::Autism spectrum disorder(ASD)is believed to have a multifactorial aetiology involving both genetics and environmental factors.Evidence also emphasises that ASD is programmed during the in ute...TToo tthhee eeddiittoorr::Autism spectrum disorder(ASD)is believed to have a multifactorial aetiology involving both genetics and environmental factors.Evidence also emphasises that ASD is programmed during the in utero period,with multiple prenatal and postnatal factors influencing the epigenome and contributing to the onset of ASD.展开更多
Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3...Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births,and for microphthalmia,it is around 14 per 100000 live births.However,combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals.Microphthalmia is reported to occur in 3.2%to 11.2%of blind children.Anophthalmia and microphthalmia(A/M)are part of a phenotypic spectrum alongside ocular coloboma,hypothesized to share a com-mon genetic basis.Both A/M can occur in isolation or as part of a syndrome.Their complex etiology involves chromosomal aberrations,monogenic inheritance pattern,and the contribution of environmental factors such as gestational-acquired infections,maternal vitamin A deficiency(VAD),exposure to X-rays,solvent misuse,and thalidomide exposure.A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far.Familial cases of A/M have a complex genetic basis,including all Mendelian modes of inheritance,i.e.,autosomal dominant,recessive,and X-linked.Most cases arise sporadically due to de novo mutations.Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M,leading to more effective diagnosis and management strategies.The present review focuses on key genetic factors,developmental abnormalities,and environmental modifiers linked with A/M.It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies,which aim to create innovative treatment options.展开更多
Retinal degeneration diseases,such as age-related macular de-generation(AMD)and retinitis pigmentosa(RP),initially mani-fest as dysfunction or death of the retinal pigment epithelium(RPE).Subretinal transplantation of...Retinal degeneration diseases,such as age-related macular de-generation(AMD)and retinitis pigmentosa(RP),initially mani-fest as dysfunction or death of the retinal pigment epithelium(RPE).Subretinal transplantation of human pluripotent stem cell(hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration.However,RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials.The development of hPSC-derived RPE cell differentiation protocols using xeno-free bio-materials is urgently needed for clinical applications.In this study,two protocols(the activin A and NIC84 protocols)were selected for modification and use in the differentiation of hiPSCs into RPE cells;the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells.The xeno-free extracellular matrix(ECM)proteins,laminin-511,laminin-521 and recombinant vitronectin,were selected as plate-coating substrates,and a Matrigel(xeno-containing ECM)-coated surface was used as a positive control.Healthy,mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons(RCS)rats,a model of retinal degeneration disease.The visual func-tion of RCS rats was evaluated by optomotor response(qOMR)and electroretinography after transplantation of hPSC-derived RPE cells.Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 pro-tocol,and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.展开更多
It is challenging to identify comorbidity patterns and mechanistically investigate disease associations based on health-related data that are often sparse,large-scale,and multimodal.Adopting a systems biology approach...It is challenging to identify comorbidity patterns and mechanistically investigate disease associations based on health-related data that are often sparse,large-scale,and multimodal.Adopting a systems biology approach,embedding-based algorithms provide a new perspective to examine diseases under a unified framework by mapping diseases into a highdimensional space as embedding vectors.These vectors and their constituted disease space encode pathological information and enable a quantitative and systemic measurement of the similarity between any pair of diseases,opening up an avenue for numerous types of downstream analyses.Here,we exemplify its potential through applications in discovering hidden disease associations,assisting in genetic parameter estimation,facilitating data-driven disease classifications,and transforming genetic association studies of diseases in consideration of comorbidities.While underscoring the power and versatility of this approach,we also discuss the challenges posed by medical context,requirements of online training and result validation,and research opportunities in constructing foundation models from multimodal disease data.With continued innovation and exploration,disease embedding has the potential to transform the fields of disease association analysis and even pathology studies by providing a holistic representation of patient health status.展开更多
Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction outcomes remains controversial. Here, we conducted a m...Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction outcomes remains controversial. Here, we conducted a meta-analysis of studies on sperm DNA damage （assessed by SCSA, TUNEL, SCD, or Comet assay） and clinical pregnancy after IVF and/or ICSI treatment from MEDLINE, EMBASE, and PUBMED database searches for this analysis. We identified 41 articles （with a total of 56 studies） including 16 IVF studies, 24 ICSI studies, and 16 mixed （IVF ＋ ICSI） studies. These studies measured DNA damage （by one of four assays： 23 SCSA, 18 TUNEL, 8 SCD, and 7 Comet） and included a total of 8068 treatment cycles （3734 IVF, 2282 ICSI, and 2052 mixed IVF ＋ ICSI）. The combined OR of 1.68 （95% Ch 1.49-1.89; P 〈 0.0001） indicates that sperm DNA damage affects clinical pregnancy following IVF and/or ICSI treatment. In addition, the combined OR estimates of IVF （16 estimates, OR = 1.65; 95% CI： 1.34-2.04; P 〈 0.0001）, ICSI （24 estimates, OR = 1.31; 95% Ch 1.08-1.59; P = 0.0068）, and mixed IVF ＋ ICSI studies （16 estimates, OR = 2.37; 95% Ch 1.89-2.97; P〈 0.0001） were also statistically significant. There is sufficient evidence in the existing literature suggesting that sperm DNA damage has a negative effect on clinical pregnancy following IVF and/or ICSI treatment.展开更多
AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treat...AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.展开更多
The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent...The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.展开更多
文摘Introduction: Turner syndrome is a rare genetic disorder characterised by the presence of one X chromosome and the absence of part or all of an X or Y chromosome and patients may experience delayed puberty and infertility. Our study aimed to evaluate the diagnostic delay in our practice and analyze the impact of this diagnostic delay on the effectiveness of patient management. Patients and Methods: Turner syndrome patients were identified from the endocrinology-diabetology nutrition department Database We examined the records of patients in whom the karyotype analysis favoured Turner syndrome. Results: We have selected 5 patients’ records of female patients with Turner syndrome. The mean age was 25, ranging from 19 to 29 years. Primary amenorrhea and characteristic dysmorphic features were observed in all patients. One married patient, who sought consultation for infertility, expressed a desire for pregnancy. Short stature was identified in 3 patients. Primary hypothyroidism and hypertension were respectively found in 1 and 2 patients. Gonadal dysgenesis was noted in 100% of cases. Karyotype analysis revealed monosomy X in 2 patients and mosaic patterns in others. All patients received estrogen-progestin treatment. Antihypertensive therapy was initiated for 2 patients. One patient is on L-thyroxine. In the short term, treatment led to the onset of menstruation after the initial months. Evaluation of treatment efficacy on internal genital organs is yet to be performed. Due to uncertain benefits at this age, growth hormone therapy was not considered for our patients. We provided counseling on assisted reproductive options for couples desiring to conceive. In our study, all patients were placed on estrogen-progestin therapy, and the response appeared favorable. Conclusion: In our practice, the diagnosis of Turner syndrome occurs very late in adulthood, at an age when growth hormone treatment is nearly ineffective. Treatment typically revolves around estrogen-progestin therapy, along with managing other comorbidities such as hypertension and primary hypothyroidism.
文摘Stem cell therapy holds great promise for the regeneration and repair of damaged tissues and organs.Stem cell therapy has been successfully applied to treat diseases that cannot be cured with conventional medicine.A careful evaluation of the outcomes is required for successful implementation of stem cell therapy.Recently,artificial intelligence(AI)has opened new avenues for research in the stem cell therapy field.The integration of AI can assist in evaluating the quality,efficiency and safety of stem cells by analyzing available data.It has the potential to improve and accelerate progress in various aspects of stem cell research and therapeutic applications.AI is still in its infancy and has certain limitations,such as algorithm validation problems,inadequate data availability,poor data quality,and ethical considerations.Considering the potential of AI to improve stem cell research and therapeutics,this review aims to explore applications of AI in understanding stem cell behavior,identification and characterization,optimization of the delivery methods,stem cell modeling and prediction of mortality risk.In addition,this review highlights the role of AI,machine learning,deep learning,and other subtypes in advancing stem cell biology research.This review also discusses the current limitations,ethical considerations,and future prospective of use of AI in stem cell research and therapeutic applications.
文摘Pediatric cancers are particularly significant due to their uncommon occurrence in children,driven by a variety of underlying factors.Because of their distinct molecular and genetic makeup,which makes early detection challenging,they are linked to problems.Diagnostic methods like imaging and tissue biopsy are only effective when the tumor has reached a size that can be identified.The liquid biopsy technique,the least intrusive and most convenient diagnostic method,is the subject of this review.It focuses on the significance of single cell analysis in examining uncommon cancer types.The many biomarkers found in bodily fluids and the cancer types they are linked to in children have been assessed,as has the potential route towards early detection and cancer recurrence forecasting.Combining the single cell liquid biopsy with the newest technologies,such as computational and multi-omics approaches,which have improved the efficiency of processing massive and unique genetic data,appears promising.This article discusses on a number of case reports for uncommon pediatric malignancies,such as Neuroblastoma,Medulloblastoma,Wilms Tumor,Rhabdomyosarcoma,Ewing Sarcoma,and Retinoblastoma,as well as their liquid biopsy profiles.Furthermore,the findings raise ethical questions regarding the therapeutic application of the technology as well as possible difficulties related to clinical translation.The likelihood that this single cell liquid biopsy will be clinically validated and eventually used as a routine diagnostic tool for uncommon pediatric cancers will rise with the realistic approach to sensitivity monitoring,specificity upgrading,and optimization.
文摘Aesthetic medicine is a branch of medicine dedicated to improve an individual’s appearance and overall visual appeal.Conventional aesthetic treatments have limitations,including the risk of complications,allergic reactions,and temporary benefits.Adipose tissue offers a promising alternative to conventional aesthetic treatments.The regenerative properties,accessibility and versatility of adipose tissue make it an attractive option for individuals seeking natural and long-lasting aesthetic results.Adipose tissue is rich source of adipose tissue derived stem cells(ASCs),growth factors and extracellular matrix.It can restore and rejuvenate the damaged and aged tissues.Adipose tissue can be used in different formats such as pure adipose tissue grafts,stromal vascular fraction,nanofat,macrofat,microfat and as a pure population of ASCs.In addition,ASC derived exosomes offer a unique cell-free therapy advantages bioactive molecules like growth factors,cytokines,and microRNAs to stimulate collagen production,improve skin texture,and address pigmentation issues.This review highlights the multifaceted potential of adipose tissue in aesthetic medicine.It discusses its diverse applications,the biological mechanisms involved,and emerging therapeutic approaches.Moreover,this review also highlights the challenges and future direction of using adipose tissue-based therapies for aesthetic treatments.
基金supported by Sidra Medicine Research Fund to Ajaz A.Bhat(grant number:SDR400190)Ammira S.Al-Shabeeb Akil(grant number:SDR400175).
文摘Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,prostate,pancreatic,esophageal adenocarcinoma,colorectal carcinoma,renal adenocarcinoma,and pre-and post-menopausal breast cancer.Obesity-induced cellular changes,such as impaired CD8^(+)T cell function,dyslipi-demia,hypercholesterolemia,insulin resistance,mild hyperglycemia,and fluctuating levels of leptin,resistin,adiponectin,and IL-6,contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes.Adipocytes release leptin,a pro-inflammatory substance that stimulates cancer cell proliferation,inflammation,and invasion,altering the tumor cell metabolic pathway.Adiponectin,an insulin-sensitizing adipokine,is typically downregulated in obese individuals.It has antipro-liferative,proapoptotic,and antiangiogenic properties,making it a potential cancer treatment.This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer,draw-ing on an extensive,though non-systematic,survey of the recent literature.This approach allows us to integrate and synthesize findings from various studies,offering a cohesive perspective on emerging themes and potential therapeutic targets.The review explores the metabolic disturbances,cellular alterations,inflammatory responses,and shifts in the tumor microenvironment that contribute to the obesity-cancer link.Finally,it discusses poten-tial therapeutic strategies aimed at disrupting these connections,offering valuable insights into future research directions and the development of targeted interventions.
基金supported by NIH/NCCAM center grant # 1P01 AT002644725-01"Center for Chinese Herbal Therapy(CHT) for Asthma"to Dr.Xiu-Min Li
文摘OBJECTIVE： Anti-asthma herbal medicine intervention （ASHMITM）, a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy. METHODS： Effects of ASHMI and its components aqueous extracts of Lingzhi （Ganoderma lucidum）, Kushen （Sophora flavescens） and Gancao （Glycyrrhiza uralensis）, on Th2 cytokine secretion by murine memory Th2 cells （D10.G4.1） and eotaxin-1 secretion by human lung fibroblast （HLF-1） cells were determined by measuring levels in culture supernatants by enzyme- linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS： Individual Lingzhi, Kushen and Gancao extracts and ASHMI （the combination of individual extracts） inhibited production of interleukin （IL）-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration （IC2s） values （mg/mL） forASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50values （mg/mL） for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-l. The interaction indices at IC^0 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC^0 values. All interaction indices were below 1 which indicated synergy. CONCLUSION： By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.
文摘Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic,epigenetic,and environmental variables.It is one of the world's fastestgrowing diseases,with 783 million adults expected to be affected by 2045.Devastating macrovascular consequences(cerebrovascular disease,cardiovascular disease,and peripheral vascular disease)and microvascular complications(like retinopathy,nephropathy,and neuropathy)increase mortality,blindness,kidney failure,and overall quality of life in individuals with diabetes.Clinical risk factors and glycemic management alone cannot predict the development of vascular problems;multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications.In the twenty-first century,technological advancements(genome-wide association studies,nextgeneration sequencing,and exome-sequencing)have led to the identification of genetic variants associated with diabetes,however,these variants can only explain a small proportion of the total heritability of the condition.In this review,we address some of the likely explanations for this"missing heritability",for diabetes such as the significance of uncommon variants,gene-environment interactions,and epigenetics.Current discoveries clinical value,management of diabetes,and future research directions are also discussed.
文摘Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Medical Genetics(WJMG)as a new member of the World series journal family!Following the completion of the Human Genome Project,medical genetic research has seen spectacular progress over the last decade.The number of genes that have been linked to Mendelian human traits has grown exponentially and currently this process is peaking with the access to robust genome-wide sequencing power.The genomics revolution is also seen for elucidation of rare and common DNA variants that increase risk for common disorders.Given this fast progress,there is an increasing need for making the results of genetics and genomics studies rapidly and freely available to the larger community.Thus,the decision for inaugurating this new journal is a timely one.The WJMG is a peer-reviewed,open-access periodical centered in all aspects of medical genetics research,with multidisciplinary coverage:from human phenotype to genetic and genomic mutations and variations to the study of pathological mechanisms.If you want to share new results of your research with a link to medical genetics with your peers,you will find the WJMG a good media to publish your papers!
文摘Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies.Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic patients.These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment.While a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant challenge.Point-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex scenarios.Although conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological aspects.Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional therapies.This article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.
文摘Characterization of an aqueous extract of human placenta, used as a licensed drug for wound healing, leads to the identification of several bioactive components including polydeoxyribonu-cleotides (PDRNs). PDRNs are mixture of DNA fragments of different molecular weight. A spectro-fluorimetric method of quantitation of PDRNs in the aqueous extract of human placenta by using ethidium bromide (EtBr) has been described here. It has been demonstrated by thin layer chromatography (TLC) followed by reversed phase HPLC that EtBr binds specifically with the PDRN fraction of the multi-component extract. The binding specificity of EtBr has been verified by the analysis of emission spectra of the extract. A concentration of 0.29 μg/ml EtBr exhibits a linear range of standard CT-DNA from 0.5 - 5 μg/ml of buffer (R2 = 0.992). The same concentration of EtBr shows a linear range of measurements of placenta extract from 5 - 35 μl/ml of buffer (R2 = 0.976). The points of the curve were the average of three sets where maximum variation observed was ±3%. PDRN content of the extract has been estimated based on the resultant fluorescence emission (after background correction) with respect to the standard calibration curve of calf thymus DNA (CT-DNA). Estimation of PDRN in a large number of batches of placenta extract (n = 100) has been done. The statistical analysis of the estimation was found to be significant and the lower and upper levels of PDRN were 158.30 and 239.03 μg/ml of the extract respectively. This easy-to-use method of estimation of PDRN in multi-component biological extract is reported for the first time. This will help in quantitation of PDRNs for other biological extracts.
文摘Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga(L.)Lam(a synonym of Visnaga daucoides Gaertn.)plant,which is used to cure various ailments.Many investigations into the bioactive properties of visnagin have been studied to date.The literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal diseases.Moreover,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates apoptosis.Thus,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical needs.The current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of action.The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.
文摘Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.
文摘TToo tthhee eeddiittoorr::Autism spectrum disorder(ASD)is believed to have a multifactorial aetiology involving both genetics and environmental factors.Evidence also emphasises that ASD is programmed during the in utero period,with multiple prenatal and postnatal factors influencing the epigenome and contributing to the onset of ASD.
文摘Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births,and for microphthalmia,it is around 14 per 100000 live births.However,combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals.Microphthalmia is reported to occur in 3.2%to 11.2%of blind children.Anophthalmia and microphthalmia(A/M)are part of a phenotypic spectrum alongside ocular coloboma,hypothesized to share a com-mon genetic basis.Both A/M can occur in isolation or as part of a syndrome.Their complex etiology involves chromosomal aberrations,monogenic inheritance pattern,and the contribution of environmental factors such as gestational-acquired infections,maternal vitamin A deficiency(VAD),exposure to X-rays,solvent misuse,and thalidomide exposure.A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far.Familial cases of A/M have a complex genetic basis,including all Mendelian modes of inheritance,i.e.,autosomal dominant,recessive,and X-linked.Most cases arise sporadically due to de novo mutations.Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M,leading to more effective diagnosis and management strategies.The present review focuses on key genetic factors,developmental abnormalities,and environmental modifiers linked with A/M.It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies,which aim to create innovative treatment options.
基金supported by the National Natural Science Foundation of China(52250710155)the National Key Research and Development Program of China(2021YFA1101200,2022YFA1105501)+6 种基金the Project of Zhejiang Provincial Natural Science Foundation of China(LQ24H120006)supported by the State Key Laboratory of Ophthalmology,Optometry and Vision Science,Wenzhou Medical University(J02-20210201)the Wenzhou Municipal Science and Technology Bureau(Y20240054,Y2023799)supported by the Veteran Hospital Project(VGHUST113-G4-4-1 and VGHUSTll2-G4-3-l)the National Defense Medical Center Project(112-NCU-TRI-01,113-NCU-TRI-01 and TSGH-A-112003)the Department of Science and Technology/Global Innovation and Technology Alliance(DST/GITA)(GITA/DST/TWN/P-105/2022)the National Science and Technology Council(112-2923-E-008-005-MY3,111-2221-E-008-007,111-2923-E-008-005-MY3).
文摘Retinal degeneration diseases,such as age-related macular de-generation(AMD)and retinitis pigmentosa(RP),initially mani-fest as dysfunction or death of the retinal pigment epithelium(RPE).Subretinal transplantation of human pluripotent stem cell(hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration.However,RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials.The development of hPSC-derived RPE cell differentiation protocols using xeno-free bio-materials is urgently needed for clinical applications.In this study,two protocols(the activin A and NIC84 protocols)were selected for modification and use in the differentiation of hiPSCs into RPE cells;the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells.The xeno-free extracellular matrix(ECM)proteins,laminin-511,laminin-521 and recombinant vitronectin,were selected as plate-coating substrates,and a Matrigel(xeno-containing ECM)-coated surface was used as a positive control.Healthy,mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons(RCS)rats,a model of retinal degeneration disease.The visual func-tion of RCS rats was evaluated by optomotor response(qOMR)and electroretinography after transplantation of hPSC-derived RPE cells.Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 pro-tocol,and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.
基金National Natural Science Foundation of China,Grant/Award Number:32470720Innovation Program of Chinese Academy of Agricultural Sciences,Grant/Award Number:CAASASTIP-2021-AGIS+13 种基金Chinese University of Hong KongGrant/Award Numbers:4937025,4937026,5501517,5501329Research Grants Council of the Hong Kong Special Administrative RegionChinaGrant/Award Number:CUHK 24204023Innovation and Technology Commission of the Hong Kong Special Administrative Region,ChinaGrant/Award Number:GHP/065/21SZRMGS in CUHK,Grant/Award Numbers:8601603,8601663Shun Hing Institute of Advanced Engineering(SHIAE),Grant/Award Number:BME-p1-24The King Abdullah University of Science and Technology Office of Research Administration,Grant/Award Numbers:REI/1/5234-01-01,REI/1/5289-01-01,REI/1/5404-01-01,REI/1/5414-01-01,REI/1/5992-01-01,URF/1/4663-01-01The King Abdullah University of Science and Technology Center of Excellence for Smart Health(KCSH)Grant/Award Number:5932The King Abdullah University of Science and Technology Center of Excellence on Generative AIGrant/Award Number:5940。
文摘It is challenging to identify comorbidity patterns and mechanistically investigate disease associations based on health-related data that are often sparse,large-scale,and multimodal.Adopting a systems biology approach,embedding-based algorithms provide a new perspective to examine diseases under a unified framework by mapping diseases into a highdimensional space as embedding vectors.These vectors and their constituted disease space encode pathological information and enable a quantitative and systemic measurement of the similarity between any pair of diseases,opening up an avenue for numerous types of downstream analyses.Here,we exemplify its potential through applications in discovering hidden disease associations,assisting in genetic parameter estimation,facilitating data-driven disease classifications,and transforming genetic association studies of diseases in consideration of comorbidities.While underscoring the power and versatility of this approach,we also discuss the challenges posed by medical context,requirements of online training and result validation,and research opportunities in constructing foundation models from multimodal disease data.With continued innovation and exploration,disease embedding has the potential to transform the fields of disease association analysis and even pathology studies by providing a holistic representation of patient health status.
文摘Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction outcomes remains controversial. Here, we conducted a meta-analysis of studies on sperm DNA damage （assessed by SCSA, TUNEL, SCD, or Comet assay） and clinical pregnancy after IVF and/or ICSI treatment from MEDLINE, EMBASE, and PUBMED database searches for this analysis. We identified 41 articles （with a total of 56 studies） including 16 IVF studies, 24 ICSI studies, and 16 mixed （IVF ＋ ICSI） studies. These studies measured DNA damage （by one of four assays： 23 SCSA, 18 TUNEL, 8 SCD, and 7 Comet） and included a total of 8068 treatment cycles （3734 IVF, 2282 ICSI, and 2052 mixed IVF ＋ ICSI）. The combined OR of 1.68 （95% Ch 1.49-1.89; P 〈 0.0001） indicates that sperm DNA damage affects clinical pregnancy following IVF and/or ICSI treatment. In addition, the combined OR estimates of IVF （16 estimates, OR = 1.65; 95% CI： 1.34-2.04; P 〈 0.0001）, ICSI （24 estimates, OR = 1.31; 95% Ch 1.08-1.59; P = 0.0068）, and mixed IVF ＋ ICSI studies （16 estimates, OR = 2.37; 95% Ch 1.89-2.97; P〈 0.0001） were also statistically significant. There is sufficient evidence in the existing literature suggesting that sperm DNA damage has a negative effect on clinical pregnancy following IVF and/or ICSI treatment.
基金by Grant-in-Aid for Scientif ic Research (Category B, No. 18390168) for K Tsukamoto by the Ministry of Education, Culture, Sports, Science and Technology of Japan
文摘AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.
基金The Cell Culture Core supported by grant No.PP1498:Neural Cell Culture Core and NIH grant No.04612 Intellectual&Developmental Disabilities.The Cell,Circuits and Systems Analysis Core is supported by NICHD award No.U54HD087101-03
文摘The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.
