Zhuoran Yang, Jiasheng Yin, Yiqing Hu, Li Zhu, You Zhou, Yaqi Zhang, Nirupama Krishnamurthi, Jieyu Jiang, Wenxian Zhou, Nitin Barman, Hao Lu, Junbo Ge
Coronary artery disease (CAD), the most common panvascular disease, can progress to chronic total occlusion (CTO). Drug-eluting stent (DES) is one of standard CAD treatments, but in-stent restenosis leading to CTO is challenging, with unclear optimal management. The efficacy of drug-coated balloons (DCB) for treating DES-related in-stent chronic total occlusion (IS-CTO) is undetermined. In this single-center retrospective cohort study of 198 patients with IS-CTO post-DES, 3-year outcomes of DCB, DES, and plain old balloon angioplasty (POBA) were compared, focusing on target vessel failure (TVF). DES showed the lowest TVF rate (DCB vs. DES vs. POBA: 31.8% vs. 17.1% vs. 51.6%, p < 0.01), mainly due to fewer revascularizations. Notably, the difference in TVF between DCB and DES became more apparent after the first year. DCB was an independent risk factor for late TVF (HRadj = 6.51, 95% confidence interval [CI] = 2.45–18.84, p < 0.01), whereas POBA for early TVF compared to DCB (HRadj = 5.01, 95% CI = 1.36–18.42, p = 0.02). While POBA-treated patients exhibited a higher target vessel myocardial infarction rate, the death rates were comparable across all cohorts. In conclusion, DES showed the lowest 3-year TVF rate, making it the most effective treatment for IS-CTO compared to DCB and POBA.
{"title":"Long-Term Clinical Outcomes of Treatments for In-Stent Chronic Total Occlusions: A Real-World Study Based on Different Strategies of Revascularization","authors":"Zhuoran Yang, Jiasheng Yin, Yiqing Hu, Li Zhu, You Zhou, Yaqi Zhang, Nirupama Krishnamurthi, Jieyu Jiang, Wenxian Zhou, Nitin Barman, Hao Lu, Junbo Ge","doi":"10.1002/mef2.70011","DOIUrl":"https://doi.org/10.1002/mef2.70011","url":null,"abstract":"<p>Coronary artery disease (CAD), the most common panvascular disease, can progress to chronic total occlusion (CTO). Drug-eluting stent (DES) is one of standard CAD treatments, but in-stent restenosis leading to CTO is challenging, with unclear optimal management. The efficacy of drug-coated balloons (DCB) for treating DES-related in-stent chronic total occlusion (IS-CTO) is undetermined. In this single-center retrospective cohort study of 198 patients with IS-CTO post-DES, 3-year outcomes of DCB, DES, and plain old balloon angioplasty (POBA) were compared, focusing on target vessel failure (TVF). DES showed the lowest TVF rate (DCB vs. DES vs. POBA: 31.8% vs. 17.1% vs. 51.6%, <i>p</i> < 0.01), mainly due to fewer revascularizations. Notably, the difference in TVF between DCB and DES became more apparent after the first year. DCB was an independent risk factor for late TVF (HR<sub>adj</sub> = 6.51, 95% confidence interval [CI] = 2.45–18.84, <i>p</i> < 0.01), whereas POBA for early TVF compared to DCB (HR<sub>adj</sub> = 5.01, 95% CI = 1.36–18.42, <i>p</i> = 0.02). While POBA-treated patients exhibited a higher target vessel myocardial infarction rate, the death rates were comparable across all cohorts. In conclusion, DES showed the lowest 3-year TVF rate, making it the most effective treatment for IS-CTO compared to DCB and POBA.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423826","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}
Immunotherapy has revolutionized cancer treatment in recent years, yet non-responsiveness of immunotherapy remains a challenge for cancer treatment. Therefore, the prediction method for potential clinical benefits of patients from immunotherapy is urgently needed. This study aims to develop an effective clinical practice assistance tool to evaluate the potential clinical benefits and therapy responsiveness of patients undergoing immunotherapy. We developed an immunotherapy resistance score (IRS), which performed well compared with conventional immunotherapy response indicators across different immunotherapy cohorts. Tumor microenvironment (TME) analysis showed that both immune and nonimmune features collectively impact immunotherapy responsiveness. Thus, IRS was constructed based on the TME features using machine learning approaches. The clinical application potential of IRS has been demonstrated in our in-house Harbin Medical University (HMU) cohort and an external validation cohort. Furthermore, we analyzed the correlation between IRS and pathways related to cancer therapy targets to explore the application potential of IRS in comprehensive cancer therapy. In conclusion, IRS is a robust tool for predicting patient immunotherapy prognosis, which has great potential to promote precise clinical therapy.
{"title":"Machine-learning-based integration of tumor microenvironment features predicting immunotherapy response","authors":"Kunpeng Luo, Shuqiang Liu, Yunfu Cui, Jinglin Li, Xiuyun Shen, Jincheng Xu, Yanan Jiang","doi":"10.1002/mef2.70009","DOIUrl":"https://doi.org/10.1002/mef2.70009","url":null,"abstract":"<p>Immunotherapy has revolutionized cancer treatment in recent years, yet non-responsiveness of immunotherapy remains a challenge for cancer treatment. Therefore, the prediction method for potential clinical benefits of patients from immunotherapy is urgently needed. This study aims to develop an effective clinical practice assistance tool to evaluate the potential clinical benefits and therapy responsiveness of patients undergoing immunotherapy. We developed an immunotherapy resistance score (IRS), which performed well compared with conventional immunotherapy response indicators across different immunotherapy cohorts. Tumor microenvironment (TME) analysis showed that both immune and nonimmune features collectively impact immunotherapy responsiveness. Thus, IRS was constructed based on the TME features using machine learning approaches. The clinical application potential of IRS has been demonstrated in our in-house Harbin Medical University (HMU) cohort and an external validation cohort. Furthermore, we analyzed the correlation between IRS and pathways related to cancer therapy targets to explore the application potential of IRS in comprehensive cancer therapy. In conclusion, IRS is a robust tool for predicting patient immunotherapy prognosis, which has great potential to promote precise clinical therapy.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143119708","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}
<p>Most individuals with COVID-19, caused by SARS-CoV-2 infection, experience asymptomatic or mild-to-moderate symptoms, while a minority of patients may deteriorate to severe illness or fatal outcomes [<span>1</span>]. Severe COVID-19 can lead to critical complications, including respiratory distress and increased mortality rates [<span>2</span>]. One such complication is the development of “white lung” on chest radiographs (e.g., X-ray), characterized by extensive inflammation and fluid accumulation affecting 70%–80% of the lung area [<span>3</span>]. The appearance of white lung signals a critical stage in COVID-19 patients, profoundly impairing lung function, often requiring mechanical ventilation and ICU admission, and substantially increasing mortality risk [<span>1, 2</span>]. Despite extensive research into the pathophysiology of COVID-19, the mechanisms underlying “white lung” remain poorly understood.</p><p>Here, we performed single-cell RNA sequencing analysis of bronchoalveolar lavage fluid (BALF) to characterize the pathophysiology of “white lung” in COVID-19 (Figure 1A). BALF samples were collected from 16 patients with moderate (MO, <i>n</i> = 3), severe (SE, <i>n</i> = 6), and “white lung” (WL, <i>n</i> = 7) syndrome, as well as from 3 healthy controls (HC) (Figure 1A). After quality control filtering (Supporting Information S1: Figure S1A–C), we obtained transcriptome data sets from 136,015 cells (mean = 7159 cells/sample). Using uniform manifold approximation and projection (UMAP), we identified 7 major cell types (Supporting Information S1: Figure S1D) and, through sub-clustering, 44 distinct cell states representing diverse respiratory cell types (Supporting Information S1: Figure S1E). UMAP visualization (Supporting Information S1: Figure S1F) revealed substantial inter-group heterogeneity. The distribution of seven major clusters was portrayed through R<sub>O/E</sub> (Supporting Information S1: Figure S1G) [<span>1</span>]. We observed an obvious expansion of NK and neutrophils in COVID-19 patients with “white lung” (Supporting Information S1: Figure S1G–J, Figure 1B). However, NK cells comprised < 0.5% of the total cell population in these patients (Supporting Information S1: Figure S1I), implying that their expansion is unlikely to be the primary driver of this complication. In contrast, neutrophils constituted up to 85% of BALF cells in COVID-19 patients with “white lung,” whereas this proportion did not exceed 25% in any other group (Figure 1B, Supporting Information S1: Figure S1H). PCA analysis clearly distinguished neutrophils from “white lung” patients from those in controls and patients with moderate and severe COVID-19 (Supporting Information S1: Figure S2A,B). Among BALF immune cells, neutrophils exhibited a significant association with “white lung” patients (Supporting Information S1: Figure S2C). These results suggested that neutrophil infiltration may be a key driver of “white lung” development in COVID-19.<
{"title":"COVID-19-Associated White Lung Correlates With the Dysfunctional Neutrophil Response Revealed by Single-Cell Immune Profiling","authors":"Yi Wang, Xiaoxia Wang, Xiong Zhu, Guogang Xu","doi":"10.1002/mef2.70012","DOIUrl":"https://doi.org/10.1002/mef2.70012","url":null,"abstract":"<p>Most individuals with COVID-19, caused by SARS-CoV-2 infection, experience asymptomatic or mild-to-moderate symptoms, while a minority of patients may deteriorate to severe illness or fatal outcomes [<span>1</span>]. Severe COVID-19 can lead to critical complications, including respiratory distress and increased mortality rates [<span>2</span>]. One such complication is the development of “white lung” on chest radiographs (e.g., X-ray), characterized by extensive inflammation and fluid accumulation affecting 70%–80% of the lung area [<span>3</span>]. The appearance of white lung signals a critical stage in COVID-19 patients, profoundly impairing lung function, often requiring mechanical ventilation and ICU admission, and substantially increasing mortality risk [<span>1, 2</span>]. Despite extensive research into the pathophysiology of COVID-19, the mechanisms underlying “white lung” remain poorly understood.</p><p>Here, we performed single-cell RNA sequencing analysis of bronchoalveolar lavage fluid (BALF) to characterize the pathophysiology of “white lung” in COVID-19 (Figure 1A). BALF samples were collected from 16 patients with moderate (MO, <i>n</i> = 3), severe (SE, <i>n</i> = 6), and “white lung” (WL, <i>n</i> = 7) syndrome, as well as from 3 healthy controls (HC) (Figure 1A). After quality control filtering (Supporting Information S1: Figure S1A–C), we obtained transcriptome data sets from 136,015 cells (mean = 7159 cells/sample). Using uniform manifold approximation and projection (UMAP), we identified 7 major cell types (Supporting Information S1: Figure S1D) and, through sub-clustering, 44 distinct cell states representing diverse respiratory cell types (Supporting Information S1: Figure S1E). UMAP visualization (Supporting Information S1: Figure S1F) revealed substantial inter-group heterogeneity. The distribution of seven major clusters was portrayed through R<sub>O/E</sub> (Supporting Information S1: Figure S1G) [<span>1</span>]. We observed an obvious expansion of NK and neutrophils in COVID-19 patients with “white lung” (Supporting Information S1: Figure S1G–J, Figure 1B). However, NK cells comprised < 0.5% of the total cell population in these patients (Supporting Information S1: Figure S1I), implying that their expansion is unlikely to be the primary driver of this complication. In contrast, neutrophils constituted up to 85% of BALF cells in COVID-19 patients with “white lung,” whereas this proportion did not exceed 25% in any other group (Figure 1B, Supporting Information S1: Figure S1H). PCA analysis clearly distinguished neutrophils from “white lung” patients from those in controls and patients with moderate and severe COVID-19 (Supporting Information S1: Figure S2A,B). Among BALF immune cells, neutrophils exhibited a significant association with “white lung” patients (Supporting Information S1: Figure S2C). These results suggested that neutrophil infiltration may be a key driver of “white lung” development in COVID-19.<","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143119709","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}
Linling Cheng, Charlotte L. Zhang, Cheryl C. Lai, Ning Sun, Hiuwa Hang
<p>Dear Editor,</p><p>Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible visual loss in older individuals and can significantly impact their quality of life and independence. Age-induced degeneration of the retinal pigment epithelium (RPE) leads to a hypoxia and chronic inflammation, which promote abnormal choroidal neovascularization (CNV) via vascular endothelial growth factor (VEGF) secretion.<span><sup>1</sup></span> This neovascularization disrupts retinal structure, causing exudation and vision impairment.</p><p>The advent of anti-VEGF agents, designed to reduce abnormal neovascularization by inhibiting VEGF, has been validated in various clinical studies. Brolucizumab (Beovu®) is a newer agent, comprising a 26 kDa humanized monoclonal single-chain variable fragment against VEGF-A, and has demonstrated comparable efficacy to existing agents in improving visual and anatomical outcomes with fewer required dosages, thereby lowering treatment burden.<span><sup>2</sup></span> In the MERLIN study, 6 mg injections of Beovu® at 4-week intervals led to more pronounced effect in reducing subretinal fluid (SRF) compared to aflibercept.<span><sup>2</sup></span> However, the safety profile of brolucizumab remains a concern due to the higher incidence of reported adverse effects in patients, including noninfectious intraocular inflammation (IOI), endophthalmitis, retinal vasculitis (RV), retinal vascular occlusion (RVO), and secondary glaucoma.<span><sup>3</sup></span></p><p>Here, we report the clinical outcomes of five nAMD patients treated with Beovu® at the Macau Brightcare Medical Center between April 2017 and February 2023. Each patient received intravitreal Beovu® or a combination of Beovu® and other anti-VEGF agents (Table S1). The outcomes of these five patients treated for nAMD and polypoidal choroidal vasculopathy (PCV) illustrate variable responses to anti-VEGF therapies, as well as the potential for adverse effects with newer treatments.</p><p>Patient 1 presented with pigment epithelial detachment (PED) (Figure S1A) and significant improvement in the right eye following a Beovu® injection (Figure S1B), achieving improved best corrected visual acuity (BCVA) from 1.0 to 1.2 at 9 days, with stability at 43 days. OCT showed progressive resolution of PED without recurrence, suggesting a favorable response to Beovu® for initial PED resolution in nAMD.</p><p>Patient 2 initially showed improvement in BCVA and reduced SRF after three Lucentis® injections (Figure S2A,B). Three years later, recurrence with significant PED and SRF required further treatment. Beovu® injections stabilized the condition (Figure S2C,D), but BCVA only improved marginally to counting fingers. While Beovu® helped reduce fluid accumulation, the visual recovery remained limited, highlighting potential limitations in achieving functional gains in recurrent cases.</p><p>Patient 3 also presented with leakage (Figure S3A) and SRF (Figure S3B) in bo
{"title":"Case series: Brolucizumab efficacy and safety in treating neovascular age-related macular degeneration","authors":"Linling Cheng, Charlotte L. Zhang, Cheryl C. Lai, Ning Sun, Hiuwa Hang","doi":"10.1002/mef2.70010","DOIUrl":"https://doi.org/10.1002/mef2.70010","url":null,"abstract":"<p>Dear Editor,</p><p>Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible visual loss in older individuals and can significantly impact their quality of life and independence. Age-induced degeneration of the retinal pigment epithelium (RPE) leads to a hypoxia and chronic inflammation, which promote abnormal choroidal neovascularization (CNV) via vascular endothelial growth factor (VEGF) secretion.<span><sup>1</sup></span> This neovascularization disrupts retinal structure, causing exudation and vision impairment.</p><p>The advent of anti-VEGF agents, designed to reduce abnormal neovascularization by inhibiting VEGF, has been validated in various clinical studies. Brolucizumab (Beovu®) is a newer agent, comprising a 26 kDa humanized monoclonal single-chain variable fragment against VEGF-A, and has demonstrated comparable efficacy to existing agents in improving visual and anatomical outcomes with fewer required dosages, thereby lowering treatment burden.<span><sup>2</sup></span> In the MERLIN study, 6 mg injections of Beovu® at 4-week intervals led to more pronounced effect in reducing subretinal fluid (SRF) compared to aflibercept.<span><sup>2</sup></span> However, the safety profile of brolucizumab remains a concern due to the higher incidence of reported adverse effects in patients, including noninfectious intraocular inflammation (IOI), endophthalmitis, retinal vasculitis (RV), retinal vascular occlusion (RVO), and secondary glaucoma.<span><sup>3</sup></span></p><p>Here, we report the clinical outcomes of five nAMD patients treated with Beovu® at the Macau Brightcare Medical Center between April 2017 and February 2023. Each patient received intravitreal Beovu® or a combination of Beovu® and other anti-VEGF agents (Table S1). The outcomes of these five patients treated for nAMD and polypoidal choroidal vasculopathy (PCV) illustrate variable responses to anti-VEGF therapies, as well as the potential for adverse effects with newer treatments.</p><p>Patient 1 presented with pigment epithelial detachment (PED) (Figure S1A) and significant improvement in the right eye following a Beovu® injection (Figure S1B), achieving improved best corrected visual acuity (BCVA) from 1.0 to 1.2 at 9 days, with stability at 43 days. OCT showed progressive resolution of PED without recurrence, suggesting a favorable response to Beovu® for initial PED resolution in nAMD.</p><p>Patient 2 initially showed improvement in BCVA and reduced SRF after three Lucentis® injections (Figure S2A,B). Three years later, recurrence with significant PED and SRF required further treatment. Beovu® injections stabilized the condition (Figure S2C,D), but BCVA only improved marginally to counting fingers. While Beovu® helped reduce fluid accumulation, the visual recovery remained limited, highlighting potential limitations in achieving functional gains in recurrent cases.</p><p>Patient 3 also presented with leakage (Figure S3A) and SRF (Figure S3B) in bo","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143114341","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}
Muscle atrophy, characterized by the loss of muscle mass and function, is a hallmark of sarcopenia and cachexia, frequently associated with aging, malignant tumors, chronic heart failure, and malnutrition. Moreover, it poses significant challenges to human health, leading to increased frailty, reduced quality of life, and heightened mortality risks. Despite extensive research on sarcopenia and cachexia, consensus in their assessment remains elusive, with inconsistent conclusions regarding their molecular mechanisms. Muscle atrophy models are crucial tools for advancing research in this field. Currently, animal models of muscle atrophy used for clinical and basic scientific studies are induced through various methods, including aging, genetic editing, nutritional modification, exercise, chronic wasting diseases, and drug administration. Muscle atrophy models also include in vitro and small organism models. Despite their value, each of these models has certain limitations. This review focuses on the limitations and diverse applications of muscle atrophy models to understand sarcopenia and cachexia, and encourage their rational use in future research, therefore deepening the understanding of underlying pathophysiological mechanisms, and ultimately advancing the exploration of therapeutic strategies for sarcopenia and cachexia.
{"title":"The recent development, application, and future prospects of muscle atrophy animal models","authors":"Gongchang Zhang, Fengjuan Hu, Tingting Huang, Xiaoqing Ma, Ying Cheng, Xiaolei Liu, Wenzhou Jiang, Birong Dong, Chenying Fu","doi":"10.1002/mef2.70008","DOIUrl":"https://doi.org/10.1002/mef2.70008","url":null,"abstract":"<p>Muscle atrophy, characterized by the loss of muscle mass and function, is a hallmark of sarcopenia and cachexia, frequently associated with aging, malignant tumors, chronic heart failure, and malnutrition. Moreover, it poses significant challenges to human health, leading to increased frailty, reduced quality of life, and heightened mortality risks. Despite extensive research on sarcopenia and cachexia, consensus in their assessment remains elusive, with inconsistent conclusions regarding their molecular mechanisms. Muscle atrophy models are crucial tools for advancing research in this field. Currently, animal models of muscle atrophy used for clinical and basic scientific studies are induced through various methods, including aging, genetic editing, nutritional modification, exercise, chronic wasting diseases, and drug administration. Muscle atrophy models also include in vitro and small organism models. Despite their value, each of these models has certain limitations. This review focuses on the limitations and diverse applications of muscle atrophy models to understand sarcopenia and cachexia, and encourage their rational use in future research, therefore deepening the understanding of underlying pathophysiological mechanisms, and ultimately advancing the exploration of therapeutic strategies for sarcopenia and cachexia.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118884","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}
Binyan Zhao, Bailing Zhou, Qing Li, Chunyan Su, Jing Ma, Li Yang
Cancer immunotherapies, developed on the basis of research into tumor escape mechanisms, manipulate the immune system to reactivate an antitumor immune response to recognize and attack cancer cells. Immunotherapy has demonstrated promising and exciting outcomes in the treatment of many cancers, yet not all patients experience favorable responses. The gut microbiota plays a critical role in modulating the host immune system, influencing responses to cancer immunotherapy. Research has increasingly demonstrated that specific microbial communities can increase the efficacy of immune checkpoint inhibitors, although the mechanisms involved remain under investigation. However, a clear gap exists in the understanding of how bacterial therapies can be further optimized for cancer treatment. This review provides an in-depth analysis of current bacterial therapies used in clinical trials as adjuncts to cancer immunotherapy, summarizing common research approaches and technologies utilized to investigate gut microbiota interactions with the immune system. Additionally, advanced strategies for modifying bacteria, including genetic engineering, surface modifications, and the development of bacterial derivatives, are discussed. By synthesizing these findings, this review highlights the potential of microbiota-based therapies to improve immunotherapy outcomes and offers future directions for improving clinical applications.
{"title":"Harnessing the gut microbiome to enhance cancer immunotherapy: Current advances and future directions in microbiota-based therapeutic strategies","authors":"Binyan Zhao, Bailing Zhou, Qing Li, Chunyan Su, Jing Ma, Li Yang","doi":"10.1002/mef2.70006","DOIUrl":"https://doi.org/10.1002/mef2.70006","url":null,"abstract":"<p>Cancer immunotherapies, developed on the basis of research into tumor escape mechanisms, manipulate the immune system to reactivate an antitumor immune response to recognize and attack cancer cells. Immunotherapy has demonstrated promising and exciting outcomes in the treatment of many cancers, yet not all patients experience favorable responses. The gut microbiota plays a critical role in modulating the host immune system, influencing responses to cancer immunotherapy. Research has increasingly demonstrated that specific microbial communities can increase the efficacy of immune checkpoint inhibitors, although the mechanisms involved remain under investigation. However, a clear gap exists in the understanding of how bacterial therapies can be further optimized for cancer treatment. This review provides an in-depth analysis of current bacterial therapies used in clinical trials as adjuncts to cancer immunotherapy, summarizing common research approaches and technologies utilized to investigate gut microbiota interactions with the immune system. Additionally, advanced strategies for modifying bacteria, including genetic engineering, surface modifications, and the development of bacterial derivatives, are discussed. By synthesizing these findings, this review highlights the potential of microbiota-based therapies to improve immunotherapy outcomes and offers future directions for improving clinical applications.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118606","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}
Hongsha Yang, Pan Song, Meidie Yu, Liming Huang, Yun Tang, Guisen Li, Yi Li, Yunlin Feng
Acute kidney injury (AKI) is a significant global healthcare burden but lacks specific and effective treatment. Renal tubular cells damage is central to ischemia-reperfusion injury (IRI) induced AKI. It is critical to clarify the initiation mechanisms of renal IRI and develop early intervention targets of AKI. This study used label-free quantification proteomic analysis to identify new targets in AKI-related renal tubular injury and investigate the potential mechanisms. We discovered significant changes in cysteinyl-tRNA synthetase (CARS) in renal tubular cell during IRI. Considering the involvement of CARS in ATP metabolism and the close correlation between ATP and pyroptosis, we further explored pyroptosis phenotype with and without CARS intervention as well as the expression of CARS during pyroptosis activation and inhibition. Our findings suggest that CARS expression decreased over time and is linked to pyroptosis. Modifying CARS affects ATP metabolism and alters the expression of pyroptosis-related proteins during H/R and IRI treatments. Regulating pyroptosis may influence CARS expression during IRI treatment. Overall, CARS is associated with renal tubular damage from ischemia-reperfusion injury, possibly involving pyroptosis, though the regulatory mechanism remains unclear.
{"title":"Cysteinyl-tRNA synthetase is involved in damage of renal tubular cells in ischemia–reperfusion-induced acute kidney injury via pyroptosis","authors":"Hongsha Yang, Pan Song, Meidie Yu, Liming Huang, Yun Tang, Guisen Li, Yi Li, Yunlin Feng","doi":"10.1002/mef2.70005","DOIUrl":"https://doi.org/10.1002/mef2.70005","url":null,"abstract":"<p>Acute kidney injury (AKI) is a significant global healthcare burden but lacks specific and effective treatment. Renal tubular cells damage is central to ischemia-reperfusion injury (IRI) induced AKI. It is critical to clarify the initiation mechanisms of renal IRI and develop early intervention targets of AKI. This study used label-free quantification proteomic analysis to identify new targets in AKI-related renal tubular injury and investigate the potential mechanisms. We discovered significant changes in cysteinyl-tRNA synthetase (CARS) in renal tubular cell during IRI. Considering the involvement of CARS in ATP metabolism and the close correlation between ATP and pyroptosis, we further explored pyroptosis phenotype with and without CARS intervention as well as the expression of CARS during pyroptosis activation and inhibition. Our findings suggest that CARS expression decreased over time and is linked to pyroptosis. Modifying CARS affects ATP metabolism and alters the expression of pyroptosis-related proteins during H/R and IRI treatments. Regulating pyroptosis may influence CARS expression during IRI treatment. Overall, CARS is associated with renal tubular damage from ischemia-reperfusion injury, possibly involving pyroptosis, though the regulatory mechanism remains unclear.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861805","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}
Huagang Peng, Yifan Rao, Weilong Shang, Yi Yang, Li Tan, Lu Liu, Zhen Hu, Yuting Wang, Xiaonan Huang, He Liu, Mengyang Li, Zuwen Guo, Juan Chen, Yuhua Yang, Jianghong Wu, Wenchang Yuan, Qiwen Hu, Xiancai Rao
Vancomycin (VAN)-intermediate Staphylococcus aureus (VISA) is a critical cause of VAN treatment failure worldwide. Multiple genetic changes are reportedly associated with VISA formation, whereas VISA strains often present common phenotypes, such as reduced autolysis and thickened cell wall. However, how mutated genes lead to VISA common phenotypes remains unclear. Here, we show a metabolism regulatory cascade (CcpA-GlmS), whereby mutated two-component systems (TCSs) link to the common phenotypes of VISA. We found that ccpA deletion decreased VAN resistance in VISA strains with diverse genetic backgrounds. Metabolic alteration in VISA was associated with ccpA upregulation, which was directly controlled by TCSs WalKR and GraSR. RNA-sequencing revealed the crucial roles of CcpA in changing the carbon flow and nitrogen flux of VISA to promote VAN resistance. A gate enzyme (GlmS) that drives carbon flow to the cell wall precursor biosynthesis was upregulated in VISA. CcpA directly controlled glmS expression. Blocking CcpA sensitized VISA strains to VAN treatment in vitro and in vivo. Overall, this work uncovers a link between the formation of VISA phenotypes and commonly mutated genes. Inhibition of CcpA-GlmS cascade is a promising strategy to restore the therapeutic efficiency of VAN against VISA infections.
万古霉素（VAN）中间金黄色葡萄球菌（VISA）是导致全球 VAN 治疗失败的一个重要原因。据报道，多种基因变化与 VISA 的形成有关，而 VISA 菌株通常具有共同的表型，如自溶减少和细胞壁增厚。然而，突变基因如何导致 VISA 的共同表型仍不清楚。在这里，我们展示了一个代谢调控级联（CcpA-GlmS），其中突变的双组分系统（TCS）与 VISA 的共同表型相关联。我们发现，在具有不同遗传背景的 VISA 菌株中，ccpA 缺失会降低 VAN 抗性。VISA 的代谢改变与 ccpA 的上调有关，而 ccpA 的上调直接受 TCS WalKR 和 GraSR 的控制。RNA 测序揭示了 CcpA 在改变 VISA 的碳流和氮流以促进 VAN 抗性方面的关键作用。在 VISA 中，一种驱动碳流进入细胞壁前体生物合成的门酶（GlmS）被上调。CcpA 直接控制着 glmS 的表达。阻断 CcpA 可使 VISA 菌株在体外和体内对 VAN 处理敏感。总之，这项研究发现了 VISA 表型的形成与常见突变基因之间的联系。抑制 CcpA-GlmS 级联是恢复 VAN 对 VISA 感染的治疗效率的一种有前途的策略。
{"title":"Vancomycin-intermediate Staphylococcus aureus employs CcpA-GlmS metabolism regulatory cascade to resist vancomycin","authors":"Huagang Peng, Yifan Rao, Weilong Shang, Yi Yang, Li Tan, Lu Liu, Zhen Hu, Yuting Wang, Xiaonan Huang, He Liu, Mengyang Li, Zuwen Guo, Juan Chen, Yuhua Yang, Jianghong Wu, Wenchang Yuan, Qiwen Hu, Xiancai Rao","doi":"10.1002/mef2.70007","DOIUrl":"https://doi.org/10.1002/mef2.70007","url":null,"abstract":"<p>Vancomycin (VAN)-intermediate <i>Staphylococcus aureus</i> (VISA) is a critical cause of VAN treatment failure worldwide. Multiple genetic changes are reportedly associated with VISA formation, whereas VISA strains often present common phenotypes, such as reduced autolysis and thickened cell wall. However, how mutated genes lead to VISA common phenotypes remains unclear. Here, we show a metabolism regulatory cascade (CcpA-GlmS), whereby mutated two-component systems (TCSs) link to the common phenotypes of VISA. We found that <i>ccpA</i> deletion decreased VAN resistance in VISA strains with diverse genetic backgrounds. Metabolic alteration in VISA was associated with <i>ccpA</i> upregulation, which was directly controlled by TCSs WalKR and GraSR. RNA-sequencing revealed the crucial roles of CcpA in changing the carbon flow and nitrogen flux of VISA to promote VAN resistance. A gate enzyme (GlmS) that drives carbon flow to the cell wall precursor biosynthesis was upregulated in VISA. CcpA directly controlled <i>glmS</i> expression. Blocking CcpA sensitized VISA strains to VAN treatment in vitro and in vivo. Overall, this work uncovers a link between the formation of VISA phenotypes and commonly mutated genes. Inhibition of CcpA-GlmS cascade is a promising strategy to restore the therapeutic efficiency of VAN against VISA infections.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861578","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}
Siyu Xia, Wenting Ye, Jiajun Zeng, Ge Song, Yan Sun, Yongmei Zhang, Xiaoqing Luo, Jing Cai, Hongjin Yu, Wenwei Pan, Jiayun Chen, Chuanbin Yang, Qingming Luo, Jigang Wang, Yali Song
Intrauterine adhesion (IUA) is a common endometrial disease caused by injury, leading to reproductive health issues. Current treatments have limited effectiveness, side effects, and high recurrence rates, especially, in severe cases. However, the underlying molecular and cellular mechanisms are largely unknown. Here we performed a comprehensive analysis by profiling integrated single-cell transcriptomes of over 72,000 individual endometrial cells, encompassing samples from both patients with IUA and those with normal endometrium. We identified changes in cell type-specific molecular signatures, including the inflammatory activation in immune cells, extensive damage in epithelial subpopulations, and the deposition of collagen secreted by fibroblasts subpopulations. Our results demonstrated activation of the TREM2+ macrophages, which displayed properties of inflammatory regulation. Annexin A1+ NK subpopulations exhibited the highest susceptibility among NK subtypes, displaying decreased cellular density and the most pronounced differential gene expression. Furthermore, we identified the matrix metallopeptidase 7 (MMP7+) and C-C motif chemokine ligand 5 (CCL5+) unciliated epithelial subtype originated from pituitary tumor-transforming gene 1 (PTTG1+) unciliated epithelium as the most vulnerable subpopulations to epithelial injury. Collectively, our study offers integrated resources of the cellular microenvironment of IUA, serving as a comprehensive cellular map of the disease in affected individuals. The insights gained from this study are expected to provide valuable resources for future diagnostic and therapeutic approaches.
宫腔内粘连（IUA）是一种常见的子宫内膜疾病，由损伤引起，导致生殖健康问题。目前的治疗方法效果有限，副作用大，复发率高，尤其是在严重的情况下。然而，潜在的分子和细胞机制在很大程度上还不为人所知。在此，我们对超过 72,000 个子宫内膜细胞的单细胞转录组进行了综合分析，其中包括 IUA 患者和正常子宫内膜患者的样本。我们发现了细胞类型特异性分子特征的变化，包括免疫细胞的炎症激活、上皮亚群的广泛损伤以及成纤维细胞亚群分泌的胶原蛋白沉积。我们的研究结果表明，TREM2+巨噬细胞被激活，显示出炎症调节的特性。在 NK 亚型中，Annexin A1+ NK 亚群表现出最高的易感性，细胞密度降低，基因表达差异最明显。此外，我们还发现基质金属肽酶 7（MMP7+）和 C-C motif 趋化因子配体 5（CCL5+）无纤毛上皮亚型是最易受上皮损伤影响的亚群，它们源自垂体肿瘤转化基因 1（PTTG1+）无纤毛上皮。总之，我们的研究提供了 IUA 细胞微环境的综合资源，可作为受影响个体疾病的全面细胞图谱。从这项研究中获得的见解有望为未来的诊断和治疗方法提供宝贵的资源。
{"title":"A single-cell transcriptomic atlas of severe intrauterine adhesion","authors":"Siyu Xia, Wenting Ye, Jiajun Zeng, Ge Song, Yan Sun, Yongmei Zhang, Xiaoqing Luo, Jing Cai, Hongjin Yu, Wenwei Pan, Jiayun Chen, Chuanbin Yang, Qingming Luo, Jigang Wang, Yali Song","doi":"10.1002/mef2.70003","DOIUrl":"https://doi.org/10.1002/mef2.70003","url":null,"abstract":"<p>Intrauterine adhesion (IUA) is a common endometrial disease caused by injury, leading to reproductive health issues. Current treatments have limited effectiveness, side effects, and high recurrence rates, especially, in severe cases. However, the underlying molecular and cellular mechanisms are largely unknown. Here we performed a comprehensive analysis by profiling integrated single-cell transcriptomes of over 72,000 individual endometrial cells, encompassing samples from both patients with IUA and those with normal endometrium. We identified changes in cell type-specific molecular signatures, including the inflammatory activation in immune cells, extensive damage in epithelial subpopulations, and the deposition of collagen secreted by fibroblasts subpopulations. Our results demonstrated activation of the TREM2<sup>+</sup> macrophages, which displayed properties of inflammatory regulation. Annexin A1<sup>+</sup> NK subpopulations exhibited the highest susceptibility among NK subtypes, displaying decreased cellular density and the most pronounced differential gene expression. Furthermore, we identified the matrix metallopeptidase 7 (MMP7<sup>+</sup>) and C-C motif chemokine ligand 5 (CCL5<sup>+</sup>) unciliated epithelial subtype originated from pituitary tumor-transforming gene 1 (PTTG1<sup>+</sup>) unciliated epithelium as the most vulnerable subpopulations to epithelial injury. Collectively, our study offers integrated resources of the cellular microenvironment of IUA, serving as a comprehensive cellular map of the disease in affected individuals. The insights gained from this study are expected to provide valuable resources for future diagnostic and therapeutic approaches.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861471","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}
Laurence Si Chong Lok, Shuvam Sarkar, Calista Chi In Lam, Chak Fun Law, Sin Teng Chau, Chun Yip Thomas Leung, Wai Hin Cheang, Ting Li, Olivia Monteiro, Daniel Tomas Baptista-Hon
Long coronavirus disease (COVID) is characterized by persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has emerged as a significant health concern. As SARS-CoV-2 evolved from the wild-type strain to the Alpha, Beta, Delta, and Omicron variants, there may be a variant-specific influence on long COVID akin to the acute disease. This review aims to summarize our current knowledge of variant-specific influences in long COVID incidence, symptom profile as well as mechanisms of pathogenesis. We highlight that long COVID incidence may be lower with the Omicron variants. The symptom profile of long COVID may also show some dependence on the different variants, with a reduction in cardiopulmonary symptoms with more recent SARS-CoV-2 variants. This heterogeneity of long COVID may also be related to the variant-specific differences in affecting the immune system, viral persistence, and autoimmunity. However, emerging data also suggest that vaccinations may play a big role in shaping the presentation of long COVID. We also highlight ongoing work on long COVID incidence and symptom profiles in populations infected only by the Omicron variants. This will be beneficial toward more useful disease definitions and the development of effective diagnostic and therapeutic strategies.
{"title":"Long COVID across SARS-CoV-2 variants: Clinical features, pathogenesis, and future directions","authors":"Laurence Si Chong Lok, Shuvam Sarkar, Calista Chi In Lam, Chak Fun Law, Sin Teng Chau, Chun Yip Thomas Leung, Wai Hin Cheang, Ting Li, Olivia Monteiro, Daniel Tomas Baptista-Hon","doi":"10.1002/mef2.70004","DOIUrl":"https://doi.org/10.1002/mef2.70004","url":null,"abstract":"<p>Long coronavirus disease (COVID) is characterized by persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has emerged as a significant health concern. As SARS-CoV-2 evolved from the wild-type strain to the Alpha, Beta, Delta, and Omicron variants, there may be a variant-specific influence on long COVID akin to the acute disease. This review aims to summarize our current knowledge of variant-specific influences in long COVID incidence, symptom profile as well as mechanisms of pathogenesis. We highlight that long COVID incidence may be lower with the Omicron variants. The symptom profile of long COVID may also show some dependence on the different variants, with a reduction in cardiopulmonary symptoms with more recent SARS-CoV-2 variants. This heterogeneity of long COVID may also be related to the variant-specific differences in affecting the immune system, viral persistence, and autoimmunity. However, emerging data also suggest that vaccinations may play a big role in shaping the presentation of long COVID. We also highlight ongoing work on long COVID incidence and symptom profiles in populations infected only by the Omicron variants. This will be beneficial toward more useful disease definitions and the development of effective diagnostic and therapeutic strategies.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860012","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}
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