Hypertension is an important risk factor for cardiovascular and cerebrovascular disease-associated death. Hypertension and its complications are the main problems that have an impact on public health at present. A portion of adults with hypertension fail to meet the recommended blood pressure (BP) treatment goals, despite strict clinical management. Those individuals requiring at least three types of antihypertensive drugs to achieve their BP goal may be classified as patients with resistant hypertension (RH). Bioelectric technology is an emerging method that functions with the help of the human body's own bioelectric system. It is widely used in auxiliary examination, pain relief and organ function rehabilitation. Bioelectrical technology, as an effective treatment for RH, has developed rapidly in recent years and mainly includes renal sympathetic denervation, carotid baroreflex activation therapy, Traditional Chinese Medicine electroacupuncture and transcutaneous electrical nerve stimulation (TENS). The present review describes the pathogenesis of hypertension and provides an understanding of bioelectrical technology as a treatment. In particular, the development of the application of TENS in RH is introduced. The aim is to provide a basis for the clinical treatment of RH and a new idea for further clinical trials in this field.
{"title":"A new use of transcutaneous electrical nerve stimulation: Role of bioelectric technology in resistant hypertension (Review).","authors":"Chenghua Wang, Pu Wang, Guoqing Qi","doi":"10.3892/br.2023.1621","DOIUrl":"https://doi.org/10.3892/br.2023.1621","url":null,"abstract":"<p><p>Hypertension is an important risk factor for cardiovascular and cerebrovascular disease-associated death. Hypertension and its complications are the main problems that have an impact on public health at present. A portion of adults with hypertension fail to meet the recommended blood pressure (BP) treatment goals, despite strict clinical management. Those individuals requiring at least three types of antihypertensive drugs to achieve their BP goal may be classified as patients with resistant hypertension (RH). Bioelectric technology is an emerging method that functions with the help of the human body's own bioelectric system. It is widely used in auxiliary examination, pain relief and organ function rehabilitation. Bioelectrical technology, as an effective treatment for RH, has developed rapidly in recent years and mainly includes renal sympathetic denervation, carotid baroreflex activation therapy, Traditional Chinese Medicine electroacupuncture and transcutaneous electrical nerve stimulation (TENS). The present review describes the pathogenesis of hypertension and provides an understanding of bioelectrical technology as a treatment. In particular, the development of the application of TENS in RH is introduced. The aim is to provide a basis for the clinical treatment of RH and a new idea for further clinical trials in this field.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 6","pages":"38"},"PeriodicalIF":2.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/72/5f/br-18-06-01621.PMC10165504.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9507687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manuel Alejandro Giraldo-Delgado, Mateo Zuluaga-Gómez, Daniel González-Arroyave, Carlos M Ardila
The electrocardiogram (ECG) changes in patients with intraparenchymal hemorrhage (IPH) have remained largely elusive and no case reports are currently available in the scientific literature. The medical management of a patient with ST-segment elevation associated with IPH was described in the present study. The case report describes a 78-year-old male patient who presented with ST-segment elevation in V1, V2, V3 and V4 on ECG. Initially, the case was managed therapeutically as an acute myocardial infarction. Later, the patient was transferred to a higher-level hospital, where a new ECG confirmed ST-segment elevation. Simple skull tomography was also performed, which revealed a spontaneous right basal ganglion in the context of an acute cerebrovascular accident of hypertensive origin. A transthoracic ECG was ordered, which revealed an ejection fraction of 65% with type I diastolic dysfunction due to relaxation disorders and without any signs of ischemia, intracavitary masses or thrombi. In addition to the presence of nonspecific ECG findings, clinicians should consider immediate brain computed tomography to confirm intracranial hemorrhage.
{"title":"ST‑segment elevation associated with intraparenchymal hemorrhage: A case report.","authors":"Manuel Alejandro Giraldo-Delgado, Mateo Zuluaga-Gómez, Daniel González-Arroyave, Carlos M Ardila","doi":"10.3892/br.2023.1622","DOIUrl":"https://doi.org/10.3892/br.2023.1622","url":null,"abstract":"<p><p>The electrocardiogram (ECG) changes in patients with intraparenchymal hemorrhage (IPH) have remained largely elusive and no case reports are currently available in the scientific literature. The medical management of a patient with ST-segment elevation associated with IPH was described in the present study. The case report describes a 78-year-old male patient who presented with ST-segment elevation in V1, V2, V3 and V4 on ECG. Initially, the case was managed therapeutically as an acute myocardial infarction. Later, the patient was transferred to a higher-level hospital, where a new ECG confirmed ST-segment elevation. Simple skull tomography was also performed, which revealed a spontaneous right basal ganglion in the context of an acute cerebrovascular accident of hypertensive origin. A transthoracic ECG was ordered, which revealed an ejection fraction of 65% with type I diastolic dysfunction due to relaxation disorders and without any signs of ischemia, intracavitary masses or thrombi. In addition to the presence of nonspecific ECG findings, clinicians should consider immediate brain computed tomography to confirm intracranial hemorrhage.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 6","pages":"39"},"PeriodicalIF":2.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189584/pdf/br-18-06-01622.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9499320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA) is one of the most common degenerative joint diseases leading to disability in the end stage. Although intra-articular triamcinolone acetonide (TA) is one of the OA treatments that have been widely used, the side effects of such corticosteroids are still controversial. Intra-articular hyaluronic acid (HA) injection is another therapeutic option for patients with OA who do not want to use corticosteroids because of their side effects. However, the difference between the histological features associated with TA and HA in the treatment of OA remains unclear. Thus, the present study aimed to compare the histological effects of TA and HA on the cartilage of patients with knee OA. In the current study, 31 patients diagnosed with grade 3-4 knee OA on the Kellgren-Lawrence radiographic grading scale were separated into three groups: TA (n=12); HA (n=7) and untreated group (n=12). Histological examination of the whole articular cartilages of the patients was performed with hematoxylin and eosin and Alcian staining, as well as using a TUNEL assay. Clinical data such as cartilage thickness, structural and component deterioration, proteoglycan levels, apoptosis and empty lacunae were compared between the three groups. The results showed a high level of deterioration in both TA and HA groups but not in the untreated group, although the thickness of cartilage in the HA group was lower compared with that in the TA and untreated groups. The proteoglycan levels in the TA group were lower compared with those in the HA group. Moreover, the number of empty lacunae in the HA group was higher compared with that in the TA group, while no difference in apoptosis was found between TA and HA groups. A significant difference was not found in the histological staining between TA and HA groups. On the other hand, a significant difference was found in cartilage deterioration between the medial and lateral sides in these groups. TA and HA groups showed comparable histological results. TA injection is cheaper and easier but has more adverse effects for patients with knee OA than HA injection. Therefore, orthopaedists should select TA or HA based on the economic and specific needs of patients.
{"title":"Histological features of knee osteoarthritis treated with triamcinolone acetonide and hyaluronic acid.","authors":"Pattaranatcha Charnwichai, Rachaneekorn Tammachote, Nattapol Tammachote, Thiamjit Chaichana, Nakarin Kitkumthorn","doi":"10.3892/br.2023.1623","DOIUrl":"https://doi.org/10.3892/br.2023.1623","url":null,"abstract":"<p><p>Osteoarthritis (OA) is one of the most common degenerative joint diseases leading to disability in the end stage. Although intra-articular triamcinolone acetonide (TA) is one of the OA treatments that have been widely used, the side effects of such corticosteroids are still controversial. Intra-articular hyaluronic acid (HA) injection is another therapeutic option for patients with OA who do not want to use corticosteroids because of their side effects. However, the difference between the histological features associated with TA and HA in the treatment of OA remains unclear. Thus, the present study aimed to compare the histological effects of TA and HA on the cartilage of patients with knee OA. In the current study, 31 patients diagnosed with grade 3-4 knee OA on the Kellgren-Lawrence radiographic grading scale were separated into three groups: TA (n=12); HA (n=7) and untreated group (n=12). Histological examination of the whole articular cartilages of the patients was performed with hematoxylin and eosin and Alcian staining, as well as using a TUNEL assay. Clinical data such as cartilage thickness, structural and component deterioration, proteoglycan levels, apoptosis and empty lacunae were compared between the three groups. The results showed a high level of deterioration in both TA and HA groups but not in the untreated group, although the thickness of cartilage in the HA group was lower compared with that in the TA and untreated groups. The proteoglycan levels in the TA group were lower compared with those in the HA group. Moreover, the number of empty lacunae in the HA group was higher compared with that in the TA group, while no difference in apoptosis was found between TA and HA groups. A significant difference was not found in the histological staining between TA and HA groups. On the other hand, a significant difference was found in cartilage deterioration between the medial and lateral sides in these groups. TA and HA groups showed comparable histological results. TA injection is cheaper and easier but has more adverse effects for patients with knee OA than HA injection. Therefore, orthopaedists should select TA or HA based on the economic and specific needs of patients.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 6","pages":"40"},"PeriodicalIF":2.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/83/br-18-06-01623.PMC10203754.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9526474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yijun He, Lin Liang, Cheng Luo, Zhi-Yong Zhang, Jiongfeng Huang
Numerous physiological processes occur following bone fracture, including inflammatory cell recruitment, vascularization, and callus formation and remodeling. In particular circumstances, such as critical bone defects or osteonecrosis, the regenerative microenvironment is compromised, rendering endogenous stem/progenitor cells incapable of fully manifesting their reparative potential. Consequently, external interventions, such as grafting or augmentation, are frequently necessary. In situ bone tissue engineering (iBTE) employs cell-free scaffolds that possess microenvironmental cues, which, upon implantation, redirect the behavior of endogenous stem/progenitor cells towards a pro-regenerative inflammatory response and reestablish angiogenesis-osteogenesis coupling. This process ultimately results in vascularized bone regeneration (VBR). In this context, a comprehensive review of the current techniques and modalities in VBR-targeted iBTE technology is provided.
{"title":"Strategies for <i>in situ</i> tissue engineering of vascularized bone regeneration (Review).","authors":"Yijun He, Lin Liang, Cheng Luo, Zhi-Yong Zhang, Jiongfeng Huang","doi":"10.3892/br.2023.1625","DOIUrl":"https://doi.org/10.3892/br.2023.1625","url":null,"abstract":"<p><p>Numerous physiological processes occur following bone fracture, including inflammatory cell recruitment, vascularization, and callus formation and remodeling. In particular circumstances, such as critical bone defects or osteonecrosis, the regenerative microenvironment is compromised, rendering endogenous stem/progenitor cells incapable of fully manifesting their reparative potential. Consequently, external interventions, such as grafting or augmentation, are frequently necessary. <i>In situ</i> bone tissue engineering (iBTE) employs cell-free scaffolds that possess microenvironmental cues, which, upon implantation, redirect the behavior of endogenous stem/progenitor cells towards a pro-regenerative inflammatory response and reestablish angiogenesis-osteogenesis coupling. This process ultimately results in vascularized bone regeneration (VBR). In this context, a comprehensive review of the current techniques and modalities in VBR-targeted iBTE technology is provided.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 6","pages":"42"},"PeriodicalIF":2.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/ae/br-18-06-01625.PMC10265129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9656524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-29eCollection Date: 2023-07-01DOI: 10.3892/br.2023.1626
Hiroshi Kobayashi
Endometriosis is characterized by the presence of endometrial-like tissue outside the uterus and is associated with an inflammatory immune response. The gut and reproductive tract microbiota constitute a protective barrier against infection by pathogens and regulate inflammatory and immune functions. This review summarizes microbiota imbalance (i.e., dysbiosis) in endometriosis and discusses how dysbiosis influences disease development. The literature was searched for studies published from inception to March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. An altered gut and reproductive tract microbiome has been reported in numerous conditions, such as inflammatory bowel disease, allergies, autoimmunity, cancer and reproductive disorders (e.g., endometriosis). Furthermore, microbial dysbiosis is a hallmark of endometriosis and is characterized by a decrease in beneficial probiotics and an increase in pathogenic microbes, which leads to a series of estrobolomic and metabolomic changes. Gut or reproductive tract microbiome dysbiosis was reported in mice, nonhuman primates, and females with endometriosis. Animal models of endometriosis demonstrated the effects of the gut microbiome on lesion growth and vice versa. The immune system mediated by the microbiota-gut-reproductive tract axis triggers an inflammatory response that damages reproductive tract tissue, which possibly leads to endometriosis. However, whether the alteration of eubiosis (a balanced microbiota) to dysbiosis is a cause or a result of endometriosis is unclear. In conclusion, this review provides an overview of the relationship between the gut and reproductive tract microbiome and endometriosis, focusing on the mechanisms by which dysbiosis may increase the risk of disease.
{"title":"Gut and reproductive tract microbiota: Insights into the pathogenesis of endometriosis (Review).","authors":"Hiroshi Kobayashi","doi":"10.3892/br.2023.1626","DOIUrl":"10.3892/br.2023.1626","url":null,"abstract":"<p><p>Endometriosis is characterized by the presence of endometrial-like tissue outside the uterus and is associated with an inflammatory immune response. The gut and reproductive tract microbiota constitute a protective barrier against infection by pathogens and regulate inflammatory and immune functions. This review summarizes microbiota imbalance (i.e., dysbiosis) in endometriosis and discusses how dysbiosis influences disease development. The literature was searched for studies published from inception to March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. An altered gut and reproductive tract microbiome has been reported in numerous conditions, such as inflammatory bowel disease, allergies, autoimmunity, cancer and reproductive disorders (e.g., endometriosis). Furthermore, microbial dysbiosis is a hallmark of endometriosis and is characterized by a decrease in beneficial probiotics and an increase in pathogenic microbes, which leads to a series of estrobolomic and metabolomic changes. Gut or reproductive tract microbiome dysbiosis was reported in mice, nonhuman primates, and females with endometriosis. Animal models of endometriosis demonstrated the effects of the gut microbiome on lesion growth and vice versa. The immune system mediated by the microbiota-gut-reproductive tract axis triggers an inflammatory response that damages reproductive tract tissue, which possibly leads to endometriosis. However, whether the alteration of eubiosis (a balanced microbiota) to dysbiosis is a cause or a result of endometriosis is unclear. In conclusion, this review provides an overview of the relationship between the gut and reproductive tract microbiome and endometriosis, focusing on the mechanisms by which dysbiosis may increase the risk of disease.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"19 1","pages":"43"},"PeriodicalIF":2.3,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/08/br-19-01-01626.PMC10265574.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9659971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-18eCollection Date: 2023-06-01DOI: 10.3892/br.2023.1624
Nawzad K Esmaeil, Abdulwahid M Salih, Zuhair D Hammood, Lana R A Pshtiwan, Ari M Abdullah, Fahmi H Kakamad, Hiwa O Abdullah, Gasha S Ahmed, Berun A Abdalla, Rawezh Q Salih
Various studies on the etiology and other aspects of granulomatous mastitis (GM) have been performed; however, a lot of controversies have arisen. The present study aimed to present the clinicopathological findings and identify the sensitivity and resistance of isolated bacteria in patients with GM. In this cross-sectional study 63 female patients with a confirmed histopathological diagnosis of GM were included. A core needle biopsy was conducted for the patients to obtain a sample for histopathological examination and bacterial culture. In total, 46 types of antibiotics were used to determine the sensitivity and resistance of each isolated bacterial species. All the medical and clinical records of the patients were acquired through the completion of a questionnaire form in person or, if necessary, through the evaluation of their medical records in the database of the relevant center. The majority of the patients were in the premenopausal or perimenopausal period. GM was unilateral in 58.7% of the patients. The most common symptom was pain, followed by fever and chills. The mean ranges of the erythrocyte sedimentation rate, C-reactive protein, IL-6, IL-17, C5a, white blood count, neutrophil-to-lymphocyte ratio, and prolactin tests were significantly elevated in comparison to the normal ranges. In total, nine different bacterial species were isolated from the bacterial culture of the core biopsy samples, and 50% of the isolated bacterial species were sensitive to trimethoprim-sulfamethoxazole. Since there is no consensus on the etiology of GM, any additional studies related to this aspect expand the current understanding of this puzzling condition.
{"title":"Clinical, microbiological, immunological and hormonal profiles of patients with granulomatous mastitis.","authors":"Nawzad K Esmaeil, Abdulwahid M Salih, Zuhair D Hammood, Lana R A Pshtiwan, Ari M Abdullah, Fahmi H Kakamad, Hiwa O Abdullah, Gasha S Ahmed, Berun A Abdalla, Rawezh Q Salih","doi":"10.3892/br.2023.1624","DOIUrl":"10.3892/br.2023.1624","url":null,"abstract":"<p><p>Various studies on the etiology and other aspects of granulomatous mastitis (GM) have been performed; however, a lot of controversies have arisen. The present study aimed to present the clinicopathological findings and identify the sensitivity and resistance of isolated bacteria in patients with GM. In this cross-sectional study 63 female patients with a confirmed histopathological diagnosis of GM were included. A core needle biopsy was conducted for the patients to obtain a sample for histopathological examination and bacterial culture. In total, 46 types of antibiotics were used to determine the sensitivity and resistance of each isolated bacterial species. All the medical and clinical records of the patients were acquired through the completion of a questionnaire form in person or, if necessary, through the evaluation of their medical records in the database of the relevant center. The majority of the patients were in the premenopausal or perimenopausal period. GM was unilateral in 58.7% of the patients. The most common symptom was pain, followed by fever and chills. The mean ranges of the erythrocyte sedimentation rate, C-reactive protein, IL-6, IL-17, C5a, white blood count, neutrophil-to-lymphocyte ratio, and prolactin tests were significantly elevated in comparison to the normal ranges. In total, nine different bacterial species were isolated from the bacterial culture of the core biopsy samples, and 50% of the isolated bacterial species were sensitive to trimethoprim-sulfamethoxazole. Since there is no consensus on the etiology of GM, any additional studies related to this aspect expand the current understanding of this puzzling condition.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 6","pages":"41"},"PeriodicalIF":2.3,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/32/br-18-06-01624.PMC10265128.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9656523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Most patients with active pulmonary tuberculosis (TB) are difficult to be differentiated from pneumonia (PN), especially those with acid-fast bacillus smear-negative (AFB-) and interferon-γ release assay-positive (IGRA+) results. Thus, the aim of the present study was to develop a risk model of low-cost and rapid test for the diagnosis of AFB- IGRA+ TB from PN. A total of 41 laboratory variables of 204 AFB- IGRA+ TB and 156 PN participants were retrospectively analyzed. Candidate variables were identified by t-statistic test and univariate logistic model. The logistic regression analysis was used to construct the multivariate risk model and nomogram with internal and external validation. A total of 13 statistically differential variables were compared between AFB- IGRA+ TB and PN by false discovery rate (FDR) and odds ratio (OR). By integrating five variables, including age, uric acid (UA), albumin (ALB), hemoglobin (Hb) and white blood cell counts (WBC), a multivariate risk model with a concordance index (C-index) of 0.7 (95% CI: 0.61, 0.8) was constructed. The nomogram showed that UA and Hb acted as protective factors with an OR <1, while age, WBC and ALB were risk factors for TB occurrence. Internal and external validation revealed that nomogram prediction was consistent with the actual observations. Collectively, it was revealed that an integration of five biomarkers (age, UA, ALB, Hb and WBC) may be used to quickly predict TB in AFB- IGRA+ clinical samples from PN.
{"title":"Construction of a risk model and deep learning network based on patients with active pulmonary tuberculosis and pulmonary inflammation.","authors":"Dechang Xu, Jiang Zeng, Fangfang Xie, Qianting Yang, Kaisong Huang, Wei Xiao, Houwen Zou, Huihua Zhang","doi":"10.3892/br.2023.1616","DOIUrl":"https://doi.org/10.3892/br.2023.1616","url":null,"abstract":"<p><p>Most patients with active pulmonary tuberculosis (TB) are difficult to be differentiated from pneumonia (PN), especially those with acid-fast bacillus smear-negative (AFB<sup>-</sup>) and interferon-γ release assay-positive (IGRA<sup>+</sup>) results. Thus, the aim of the present study was to develop a risk model of low-cost and rapid test for the diagnosis of AFB<sup>-</sup> IGRA<sup>+</sup> TB from PN. A total of 41 laboratory variables of 204 AFB<sup>-</sup> IGRA<sup>+</sup> TB and 156 PN participants were retrospectively analyzed. Candidate variables were identified by t-statistic test and univariate logistic model. The logistic regression analysis was used to construct the multivariate risk model and nomogram with internal and external validation. A total of 13 statistically differential variables were compared between AFB<sup>-</sup> IGRA<sup>+</sup> TB and PN by false discovery rate (FDR) and odds ratio (OR). By integrating five variables, including age, uric acid (UA), albumin (ALB), hemoglobin (Hb) and white blood cell counts (WBC), a multivariate risk model with a concordance index (C-index) of 0.7 (95% CI: 0.61, 0.8) was constructed. The nomogram showed that UA and Hb acted as protective factors with an OR <1, while age, WBC and ALB were risk factors for TB occurrence. Internal and external validation revealed that nomogram prediction was consistent with the actual observations. Collectively, it was revealed that an integration of five biomarkers (age, UA, ALB, Hb and WBC) may be used to quickly predict TB in AFB<sup>-</sup> IGRA<sup>+</sup> clinical samples from PN.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 5","pages":"34"},"PeriodicalIF":2.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/22/br-18-05-01616.PMC10079808.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9326584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Systemic chemotherapy, the standard first-line treatment option for patients with advanced oesophageal squamous cell carcinoma (OSCC), results in a median survival of ~1 year. Immune checkpoint inhibitors are a breakthrough oncology treatment option; however, most patients with advanced OSCC develop primary and acquired resistance to programmed death receptor-1 (PD-1) monoclonal antibody, severely affecting their prognosis. Therefore, there is an urgent need to investigate the molecular mechanism underlying resistance to treatment. The present study aimed to explore the mechanism of resistance to PD-1 monoclonal antibody. Plasma samples were collected from patients with OSCC treated with immunotherapy, who achieved pathological response/partial response (CR/PR) or stable disease/progressive disease (SD/PD) after the fourth treatment cycle. TM-widely targeted metabolomics, widely targeted lipidomics, and DIA proteomics assays were performed. Differential metabolites were screened based on fold change (FC) ≥1.5 or ≤0.67 and a VIP ≥1; differential proteins were screened based on FC >1.5 or <0.67 and P<0.05. The identified metabolites were annotated and mapped using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. The differential proteins were annotated to the Gene Ontology and KEGG pathway databases. A correlation network diagram was drawn using differential expressed proteins and metabolites with (Pearson correlation coefficient) r>0.80 and P<0.05. Finally, 197 and 113 differential metabolites and proteins were screened, respectively, in patients with CR/PR and SD/PD groups. The KEGG enrichment analysis revealed that all of these metabolites and proteins were enriched in cholesterol metabolism and in the NF-κB and phospholipase D signalling pathways. The present study is the first to demonstrate that PD-1 inhibitor resistance may be attributed to cholesterol metabolism or NF-κB and phospholipase D signalling pathway activation. This finding suggests that targeting these signalling pathways may be a promising novel therapeutic approach in OSCC which may improve prognosis in patients undergoing immunotherapy.
{"title":"A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma.","authors":"Lijuan Gao, Yongshun Chen","doi":"10.3892/br.2023.1619","DOIUrl":"https://doi.org/10.3892/br.2023.1619","url":null,"abstract":"<p><p>Systemic chemotherapy, the standard first-line treatment option for patients with advanced oesophageal squamous cell carcinoma (OSCC), results in a median survival of ~1 year. Immune checkpoint inhibitors are a breakthrough oncology treatment option; however, most patients with advanced OSCC develop primary and acquired resistance to programmed death receptor-1 (PD-1) monoclonal antibody, severely affecting their prognosis. Therefore, there is an urgent need to investigate the molecular mechanism underlying resistance to treatment. The present study aimed to explore the mechanism of resistance to PD-1 monoclonal antibody. Plasma samples were collected from patients with OSCC treated with immunotherapy, who achieved pathological response/partial response (CR/PR) or stable disease/progressive disease (SD/PD) after the fourth treatment cycle. TM-widely targeted metabolomics, widely targeted lipidomics, and DIA proteomics assays were performed. Differential metabolites were screened based on fold change (FC) ≥1.5 or ≤0.67 and a VIP ≥1; differential proteins were screened based on FC >1.5 or <0.67 and P<0.05. The identified metabolites were annotated and mapped using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. The differential proteins were annotated to the Gene Ontology and KEGG pathway databases. A correlation network diagram was drawn using differential expressed proteins and metabolites with (Pearson correlation coefficient) r>0.80 and P<0.05. Finally, 197 and 113 differential metabolites and proteins were screened, respectively, in patients with CR/PR and SD/PD groups. The KEGG enrichment analysis revealed that all of these metabolites and proteins were enriched in cholesterol metabolism and in the NF-κB and phospholipase D signalling pathways. The present study is the first to demonstrate that PD-1 inhibitor resistance may be attributed to cholesterol metabolism or NF-κB and phospholipase D signalling pathway activation. This finding suggests that targeting these signalling pathways may be a promising novel therapeutic approach in OSCC which may improve prognosis in patients undergoing immunotherapy.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 5","pages":"36"},"PeriodicalIF":2.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10119673/pdf/br-18-05-01619.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anindita Tripathy, Poornachandra Yedla, Ravikanth V Vishnubhotla, Anuradha Sekaran, Sai Ram Keithi Reddy
Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease with rapid development to end stage renal disease, requiring renal replacement therapy. Genome-wide studies suggest geographical variations in genetic susceptibility to IgAN and disease progression. Specific 'candidate genes' were indicated to correlate with different functions that are involved in the pathogenesis of renal conditions. MicroRNAs (miRNAs/miRs) have a major role in mRNA degradation or translation repression, thereby regulating the expression of their target proteins. Previously, a small number of miRNAs were reported to have direct associations with IgAN. In the present study, new miRNAs linked to IgAN were identified in the Indian population. The miRNA was isolated from kidney biopsies of patients with IgAN (n=6) and healthy control tissue from patients with renal cell carcinoma (n=6). The sequencing results indicated that the miRNA percentage acquired from controls and patients with IgAN was 5.61 and 4.35%, respectively. From the results, 10 upregulated and 15 downregulated miRNAs were identified. Of the 25 differentially expressed miRNAs (DEMs), miR-181a-5p, miR-28-3p, let-7g-5p, miR-92a-3p and miR-30c-5p were not reported previously. Furthermore, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses suggested that the target genes of the DEMs were mainly enriched in pathways such as cancer, ErbB signalling, proteoglycans in cancer, Hippo signalling and MAPK pathways. The newly identified miRNAs may impact the behaviour of tissues or IgA deposition by regulating signalling pathways, which forms a basis for future studies aimed at improving the diagnosis and care of patients with IgAN in the Indian community.
{"title":"MicroRNAs as a therapeutic target in IgA nephropathy in Indian population.","authors":"Anindita Tripathy, Poornachandra Yedla, Ravikanth V Vishnubhotla, Anuradha Sekaran, Sai Ram Keithi Reddy","doi":"10.3892/br.2023.1617","DOIUrl":"https://doi.org/10.3892/br.2023.1617","url":null,"abstract":"<p><p>Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease with rapid development to end stage renal disease, requiring renal replacement therapy. Genome-wide studies suggest geographical variations in genetic susceptibility to IgAN and disease progression. Specific 'candidate genes' were indicated to correlate with different functions that are involved in the pathogenesis of renal conditions. MicroRNAs (miRNAs/miRs) have a major role in mRNA degradation or translation repression, thereby regulating the expression of their target proteins. Previously, a small number of miRNAs were reported to have direct associations with IgAN. In the present study, new miRNAs linked to IgAN were identified in the Indian population. The miRNA was isolated from kidney biopsies of patients with IgAN (n=6) and healthy control tissue from patients with renal cell carcinoma (n=6). The sequencing results indicated that the miRNA percentage acquired from controls and patients with IgAN was 5.61 and 4.35%, respectively. From the results, 10 upregulated and 15 downregulated miRNAs were identified. Of the 25 differentially expressed miRNAs (DEMs), miR-181a-5p, miR-28-3p, let-7g-5p, miR-92a-3p and miR-30c-5p were not reported previously. Furthermore, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses suggested that the target genes of the DEMs were mainly enriched in pathways such as cancer, ErbB signalling, proteoglycans in cancer, Hippo signalling and MAPK pathways. The newly identified miRNAs may impact the behaviour of tissues or IgA deposition by regulating signalling pathways, which forms a basis for future studies aimed at improving the diagnosis and care of patients with IgAN in the Indian community.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 5","pages":"35"},"PeriodicalIF":2.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/02/br-18-05-01617.PMC10119669.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aim of the present study was to investigate the protective effect of Gastrodia elata Blume (GEB) against Caenorhabditis elegans (C. elegans) in Alzheimer's disease (AD) through network pharmacology. Firstly, the active constituents of GEB through ETCM and BATMAN-TCM databases were collected and its potential AD-related targets in Swiss Target Prediction were predicted. The potential targets related to AD were collected from the GeneCards, OMIM, CTD and DisGeNET databases, and the differential genes (DEGs) between the normal population and the AD patient population in GSE5281 chip of the Gene Expression Omnibus database were collected at the same time. The intersection of the three targets yielded 59 key targets of GEB for the treatment of AD. The drug-active ingredient-target-AD network diagram was constructed and visualized with Cytoscape software to obtain the core components. Subsequently, protein-protein interaction analysis (PPI) was performed on 59 key targets through STRING database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses was performed on 59 key targets. Finally, molecular docking was conducted between core components and core targets using AutoDock software, and the C. elegans AD model was used for experimental verification to explore the regulatory paralysis effect of core components on the C. elegans model, β-amyloid (Aβ) plaque deposition, and quantitative polymerase chain reaction verification of the regulatory effect of components on targets. The GEB components 4,4'-dihydroxydiphenyl methane (DM) and protocatechuic aldehyde (PA) were found to be most strongly associated with AD, and five core targets were identified in the PPI network, including GAPDH, EP300, HSP90AB1, KDM6B, and CREBBP. In addition to GAPDH, the other four targets were successfully docked with DM and PA using AutoDock software. Compared with the control group, 0.5 mM DM and 0.25 mM PA significantly delayed C. elegans paralysis (P<0.01), and inhibited the aggregation of Aβ plaques in C. elegans. Both DM and PA could upregulate the expression level of core target gene HSP90AB1 (P<0.01), and DM upregulated the expression of KDM6B (P<0.01), suggesting that DM and PA may be potential active components of GEB in the treatment of AD.
本研究旨在通过网络药理学研究天麻(Gastrodia elata Blume, GEB)对秀丽隐杆线虫(Caenorhabditis elegans, C. elegans)对阿尔茨海默病(AD)的保护作用。首先,通过ETCM和BATMAN-TCM数据库收集GEB的有效成分,并在Swiss Target Prediction中预测其潜在ad相关靶标。从GeneCards、OMIM、CTD和DisGeNET数据库中收集与AD相关的潜在靶点,同时在Gene Expression Omnibus数据库的GSE5281芯片中收集正常人群与AD患者群体之间的差异基因(DEGs)。这三个靶点的交集产生了59个GEB治疗AD的关键靶点。利用Cytoscape软件构建药物活性成分-靶点- ad网络图并进行可视化,得到核心成分。随后,通过STRING数据库对59个关键靶点进行蛋白-蛋白互作分析(protein-protein interaction analysis, PPI),并对59个关键靶点进行基因本体和京都基因与基因组百科全书分析。最后利用AutoDock软件对核心组分与核心靶点进行分子对接,并利用秀丽隐杆线虫AD模型进行实验验证,探索核心组分对秀丽隐杆线虫模型、β-淀粉样蛋白(Aβ)斑块沉积的调控瘫痪作用,定量聚合酶链反应验证组分对靶点的调控作用。发现GEB组分4,4'-二羟基二苯甲烷(DM)和原儿茶醛(PA)与AD的相关性最强,并在PPI网络中鉴定出5个核心靶点,包括GAPDH、EP300、HSP90AB1、KDM6B和CREBBP。除GAPDH外,其他4个靶标均通过AutoDock软件与DM和PA成功对接。与对照组相比,0.5 mM DM和0.25 mM PA显著延缓秀丽隐杆线虫麻痹(PC)。线虫。DM和PA均可上调核心靶基因HSP90AB1的表达水平
{"title":"Protective effect of <i>Gastrodia elata</i> Blume in a Caenorhabditis elegans model of Alzheimer's disease based on network pharmacology.","authors":"Xiongfei Shi, Yuan Luo, Liping Yang, Xiaohua Duan","doi":"10.3892/br.2023.1620","DOIUrl":"https://doi.org/10.3892/br.2023.1620","url":null,"abstract":"<p><p>The aim of the present study was to investigate the protective effect of <i>Gastrodia elata</i> Blume (GEB) against <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) in Alzheimer's disease (AD) through network pharmacology. Firstly, the active constituents of GEB through ETCM and BATMAN-TCM databases were collected and its potential AD-related targets in Swiss Target Prediction were predicted. The potential targets related to AD were collected from the GeneCards, OMIM, CTD and DisGeNET databases, and the differential genes (DEGs) between the normal population and the AD patient population in GSE5281 chip of the Gene Expression Omnibus database were collected at the same time. The intersection of the three targets yielded 59 key targets of GEB for the treatment of AD. The drug-active ingredient-target-AD network diagram was constructed and visualized with Cytoscape software to obtain the core components. Subsequently, protein-protein interaction analysis (PPI) was performed on 59 key targets through STRING database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses was performed on 59 key targets. Finally, molecular docking was conducted between core components and core targets using AutoDock software, and the <i>C. elegans</i> AD model was used for experimental verification to explore the regulatory paralysis effect of core components on the <i>C. elegans</i> model, β-amyloid (Aβ) plaque deposition, and quantitative polymerase chain reaction verification of the regulatory effect of components on targets. The GEB components 4,4'-dihydroxydiphenyl methane (DM) and protocatechuic aldehyde (PA) were found to be most strongly associated with AD, and five core targets were identified in the PPI network, including GAPDH, EP300, HSP90AB1, KDM6B, and CREBBP. In addition to GAPDH, the other four targets were successfully docked with DM and PA using AutoDock software. Compared with the control group, 0.5 mM DM and 0.25 mM PA significantly delayed <i>C. elegans</i> paralysis (P<0.01), and inhibited the aggregation of Aβ plaques in <i>C. elegans</i>. Both DM and PA could upregulate the expression level of core target gene HSP90AB1 (P<0.01), and DM upregulated the expression of KDM6B (P<0.01), suggesting that DM and PA may be potential active components of GEB in the treatment of AD.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 5","pages":"37"},"PeriodicalIF":2.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/a5/br-18-05-01620.PMC10126622.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9718445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}