tbuckley/cabot-search huggingface dataset:
Bacteriophages from treatment-naïve type 2 diabetes individuals drive an inflammatory response in human co-cultures of dendritic cells and T cells
Authors: Torsten P. M. Scheithauer, Koen Wortelboer, Maaike Winkelmeijer, Xanthe Verdoes, Ömrüm Aydin, Yair I. Z. Acherman, Maurits L. de Brauw, Max Nieuwdorp, Elena Rampanelli, Patrick A. de Jonge, Hilde Herrema
Journal: Gut Microbes (2024)

Individuals with type 2 diabetes (T2D) show signs of low-grade inflammation, which is related to the development of insulin resistance and beta-cell dysfunction. However, the underlying triggers remain unknown. The gut microbiota is a plausible source as it comprises pro-inflammatory bacteria, bacterial metabolites and viruses, including (bacterio)phages. These prokaryotic viruses have been shown to mediate inflammatory responses in gastrointestinal disease. Given the differences in phage populations in healthy individuals versus those with cardiometabolic diseases such as T2D, we here questioned whether phages from T2D individuals would have increased immunogenic potential. To address this, we isolated intestinal phages from a fresh stool sample of healthy controls and individuals with newly diagnosed, treatment-naive T2D. Phages were purified using cesium chloride ultracentrifugation and incubated with healthy donor dendritic cells (DCs) and autologous T cells. Donors with T2D had slightly higher free viral particle numbers compared to healthy controls (p = .1972), which has been previously associated with disease states. Further, phages from T2D induced a higher inflammatory response in DCs and T cells than phages from HC. For example, the expression of the co-stimulatory molecule CD86 on DCs (p < .001) and interferon-y secretion from T cells (p < .01) were increased when comparing the two groups. These results suggest that phages might play a role in low-grade inflammation in T2D individuals.
Gut microbiota metabolite indole-3-acetic acid maintains intestinal epithelial homeostasis through mucin sulfation
Authors: Mengfan Li, Yiyun Ding, Jingge Wei, Yue Dong, Jingyi Wang, Xin Dai, Jing Yan, Feifei Chu, Kexin Zhang, Fanyi Meng, Jiahui Ma, Weilong Zhong, Bangmao Wang, Yunhuan Gao, Rongcun Yang, Xinjuan Liu, Xiaomin Su, Hailong Cao
Journal: Gut Microbes (2024)

The global incidence and prevalence of inflammatory bowel disease (IBD) are gradually increasing. A high-fat diet (HFD) is known to disrupt intestinal homeostasis and aggravate IBD, yet the underlying mechanisms remain largely undefined. Here, a positive correlation between dietary fat intake and disease severity in both IBD patients and murine colitis models is observed. A HFD induces a significant decrease in indole-3-acetic acid (IAA) and leads to intestinal barrier damage. Furthermore, IAA supplementation enhances intestinal mucin sulfation and effectively alleviates colitis. Mechanistically, IAA upregulates key molecules involved in mucin sulfation, including 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (Papss2) and solute carrier family 35 member B3 (Slc35b3), the synthesis enzyme and the transferase of 3'-phosphoadenosine-5'-phosphosulfate (PAPS), via the aryl hydrocarbon receptor (AHR). More importantly, AHR can directly bind to the transcription start site of Papss2. Oral administration of Lactobacillus reuteri, which can produce IAA, contributes to protecting against colitis and promoting mucin sulfation, while the modified L. reuteri strain lacking the iaaM gene (LactobacillusΔiaaM) and the ability to produce IAA fail to exhibit such effects. Overall, IAA enhances intestinal mucin sulfation through the AHR-Papss2-Slc35b3 pathway, contributing to the protection of intestinal homfeostasis.
Development of potent pan‐coronavirus fusion inhibitors with a new design strategy
Authors: Yuanmei Zhu, Zhongcai Gao, Xiaoli Feng, Lin Cheng, Nian Liu, Chao Liu, Shaowei Han, Qiaojiang Yang, Qingcui Zou, Huihui Chong, Zheng Zhang, Minghua Li, Gengshen Song, Yuxian He
Journal: MedComm (2024)

Abstract Development of potent and broad‐spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains one of the top priorities, especially in the cases of the emergence of mutant viruses and inability of current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion‐inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, we report its design strategy and preclinical data. First, we surprisingly found that IPB29 with a rigid linker between the peptide sequence and lipid molecule had greatly improved α‐helical structure and antiviral activity. Second, IPB29 potently inhibited a large panel of SARS‐CoV‐2 variants including the previously and currently circulating viruses, such as Omicron XBB.5.1 and EG.5.1. Third, IPB29 could also cross‐neutralize the bat‐ and pangolin‐isolated SARS‐CoV‐2‐related CoVs (RatG13, PCoV‐GD, and PCoV‐GX) and other human CoVs (SARS‐CoV, MERS‐CoV, HCoV‐NL63, and HCoV‐229E). Fourth, IPB29 administrated as an inhalation solution (IPB29‐IS) in Syrian hamsters exhibited high therapeutic and preventive efficacies against SARS‐CoV‐2 Delta or Omicron variant. Fifth, the pharmacokinetic profiles and safety pharmacology of IPB29‐IS were extensively characterized, providing data to support its evaluation in humans. In conclusion, our studies have demonstrated a novel design strategy for viral fusion inhibitors and offered an ideal drug candidate against SARS‐CoV‐2 and other coronaviruses.
The role of mesenchymal stem cells in cancer and prospects for their use in cancer therapeutics
Authors: Jian Tang, Yu Chen, Chunhua Wang, Ying Xia, Tingyu Yu, Mengjun Tang, Kun Meng, Lijuan Yin, Yang Yang, Liang Shen, Hui Xing, Xiaogang Mao
Journal: MedComm (2024)

Abstract Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC‐derived extracellular vesicles (MSCs‐EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs‐EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs‐EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs‐EVs in cancer treatment, along with the challenges they face.
Antibody–drug conjugates in cancer therapy: mechanisms and clinical studies
Authors: Jun He, Xianghua Zeng, Chunmei Wang, Enwen Wang, Yongsheng Li
Journal: MedComm (2024)

Abstract Antibody–drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies’ targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored for various tumor indications and some already approved for clinical use, challenges such as resistance due to factors like antigen expression, ADC processing, and payload have emerged. This review aims to outline the history of ADC development, their structure, mechanism of action, recent composition advancements, target selection, completed and ongoing clinical trials, resistance mechanisms, and intervention strategies. Additionally, it will delve into the potential of ADCs with novel markers, linkers, payloads, and innovative action mechanisms to enhance cancer treatment options. The evolution of ADCs has also led to the emergence of combination therapy as a new therapeutic approach to improve drug efficacy.
Eosinophils Respond to Extracellular Matrix Treated Muscle Injuries but are Not Required for Macrophage Polarization
Authors: Ravi Lokwani, Daphna Fertil, Devon R. Hartigan, Aditya Josyula, Tran B. Ngo, Kaitlyn Sadtler
Journal: Advanced Healthcare Materials (2024)

Abstract The immune response to decellularized extracellular matrix (ECM) muscle injury is characterized by Th2 T cells, Tregs, M2‐like macrophages, and an abundance of eosinophils. Eosinophils have previously been described as mediators of muscle regeneration but inhibit skin wound healing. In addition to response to wounding, a large number of eosinophils respond to biomaterial‐treated muscle injury, specifically in response to decellularized ECM. ECM treatment of muscle wounds has been associated with positive outcomes in tissue regeneration, but the detailed mechanisms of action are still being evaluated. Here, this work investigates the role of these eosinophils in terms of their immunologic phenotype and subsequent effect on the local tissue microenvironment. These cells have a mixed phenotype showing both type‐2 and regulatory gene upregulation and but are not required for macrophage polarization. Beyond the local tissue, ECM treatment is seen to induce a transient flux of eosinophils to the lungs but prevented a trauma‐associated neutrophilia in the lungs of injured mice. This work believes this local and systemic immunomodulation contributes to the regenerative effects of the material and such distal tissue effects should be considered in therapeutic design and implementation.
Advancements of Porphyrin‐Derived Nanomaterials for Antibacterial Photodynamic Therapy and Biofilm Eradication
Authors: Suwen Chen, Baoxuan Huang, Jia Tian, Weian Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract The threat posed by antibiotic‐resistant bacteria and the challenge of biofilm formation has highlighted the inadequacies of conventional antibacterial therapies, leading to increased interest in antibacterial photodynamic therapy (aPDT) in recent years. This approach offers advantages such as minimal invasiveness, low systemic toxicity, and notable effectiveness against drug‐resistant bacterial strains. Porphyrins and their derivatives, known for their high molar extinction coefficients and singlet oxygen quantum yields, have emerged as crucial photosensitizers in aPDT. However, their practical application is hindered by challenges such as poor water solubility and aggregation‐induced quenching. To address these limitations, extensive research has focused on the development of porphyrin‐based nanomaterials for aPDT, enhancing the efficacy of photodynamic sterilization and broadening the range of antimicrobial activity. This review provides an overview of various porphyrin‐based nanomaterials utilized in aPDT and biofilm eradication in recent years, including porphyrin‐loaded inorganic nanoparticles, porphyrin‐based polymer assemblies, supramolecular assemblies, metal–organic frameworks (MOFs), and covalent organic frameworks (COFs). Additionally, insights into the prospects of aPDT is offered, highlighting its potential for practical implementation.
Controlled Release of Ceria and Ferric Oxide Nanoparticles via Collagen Hydrogel for Enhanced Osteoarthritis Therapy
Authors: Xian Chen, Lili Wang, Jingting Zhang, Huiyu Yan, Shenghong Wang, Jianxi Xiao
Journal: Advanced Healthcare Materials (2024)

Abstract Osteoarthritis (OA), characterized by chronic inflammation and cartilage degeneration, significantly affects over 500 million people globally. Nanoparticles have emerged as promising treatments for OA; however, current strategies often employ a single type of nanoparticle targeting specific disease stages, limiting sustained therapeutic efficacy. In this study, a novel collagen hydrogel is introduced, thiol crosslinked collagen‐cerium oxide‐poly(D,L‐lactic‐co‐glycolic acid) microspheres encapsulating nanoparticles (CSH‐CeO 2 ‐pFe 2 O 3 ), designed for the controlled release of cerium oxide (CeO 2 ) and ferric oxide (Fe 2 O 3 ) nanoparticles for comprehensive OA management. The sulfhydryl cross‐linked collagen matrix embeds CeO 2 nanoparticles and poly(D,L‐lactic‐co‐glycolic acid) (PLGA) microspheres encapsulating Fe 2 O 3 nanoparticles. The CSH‐CeO 2 ‐pFe 2 O 3 hydrogel exhibits enhanced mechanical strength and remarkable injectability, along with a significant promotion of cell adhesion, proliferation, and chondrogenic differentiation. Notably, the hydrogel demonstrates intelligent responsiveness to high levels of reactive oxygen species, initiating the rapid release of CeO 2 nanoparticles to address the intense inflammatory responses of early‐stage OA, followed by the sustained release of Fe 2 O 3 nanoparticles to facilitate cartilage regeneration during the proliferative phase. In a rat model with cartilage defects, the hydrogel significantly alleviates inflammation and enhances cartilage regeneration, holding substantial potential for effectively managing the pathologically complex OA.
Blood-Based Biomarkers for Alzheimer Disease—Ready for Primary Care?
Authors: Lawren VandeVrede, Gil D. Rabinovici
Journal: JAMA Neurology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Unexpected extraluminal omental bleeding during endoscopic full-thickness resection for a gastric subepithelial lesion
Authors: Chaoqin Wang, Suhuan Liao, Silin Huang, Bo Li, Guang Yang, Jianzhen Ren, RenJie Chang
Journal: Endoscopy (2024)

Endoscopic full-thickness resection (EFTR) has become the treatment of choice for subepithelial lesions (SELs) that originate from the muscularis propria and/or exhibit exophytic growth patterns [1]. Bleeding is a recognized risk associated with endoscopic resection procedures, occurring both intraoperatively and postoperatively, predominantly from the resection site [2], with electrocoagulation a well-established technique for achieving hemostasis [3] [4]. There have been no previous reports of omental bleeding caused by EFTR. We report a case of extraluminal omental bleeding induced during EFTR for a gastric SEL, which was successfully managed with endoscopic hemostasis ([Video 1]).
Direct electrohydraulic lithotripsy with a novel peroral cholangioscope through the overtube for surgically-altered anatomy
Authors: Kosuke Hiroe, Shuhei Shintani, Takuya Okamoto, Hidenori Kimura, Takaaki Eguchi, Yoshihisa Tsuji, Osamu Inatomi
Journal: Endoscopy (2024)

Endoscopic management of choledocholithiasis in patients with surgically altered anatomy is challenging and likely to be difficult [1] [2]. Although the mother–baby type of peroral cholangioscopy is a useful modality, there are some limitations when using the mother scope, related to the working channel diameter and extended scope length [3] [4]. In this video, we present a direct electrohydraulic lithotripsy (EHL) using a novel type of cholangioscope without a mother scope in a patient with Roux-en-Y reconstruction.
Mechanical failure of a curved linear array echoendoscope: loose fixation of the high frequency transducer
Authors: Junichi Kaneko, Hiroki Tamakoshi, Tomoyuki Niwa, Masaki Takinami, Masafumi Nishino, Yurimi Takahashi, Takanori Yamada
Journal: Endoscopy (2024)

Endoscopic ultrasound (EUS), a well-established diagnostic modality, allows for visualization of previously inaccessible anatomical regions and enables tissue acquisition and therapeutic procedures [1] [2]. In interventional EUS, a curved linear array echoendoscope is first used to visualize an object with a high frequency transducer at the echoendoscope tip. A dedicated needle is then used to puncture the object under ultrasound guidance [3]. If fixation of the high frequency transducer becomes loose and rotates, it becomes difficult to visualize the puncture needle. We describe a case and in vitro studies showing the effect of mechanical failure of an echoendoscope ([Video 1]).
Successful gastroduodenal stenting using the endoscopic ultrasound-guided rendezvous technique by Treitz ligament puncture
Authors: Shin Yagi, Susumu Hijioka, Kohei Okamoto, Yoshikuni Nagashio, Mark Chatto, Yutaka Saito, Takuji Okusaka
Journal: Endoscopy (2024)

Endoscopic gastroduodenal stenting is a widely performed treatment for malignant gastric outlet obstruction (GOO); however, occasionally, the guidewire cannot be passed through the stenosis [1] [2] [3]. Here, we report a case of successful gastroduodenal stenting using the rendezvous technique with endoscopic ultrasound (EUS) for malignant GOO, which we believe to be the first report of gastroduodenal stenting using the rendezvous technique with EUS.
Integrated cholangioscopy-assisted lithotripsy and a novel basket approach for managing complex cystic duct confluence stones
Authors: Yasuhiro Kuraishi, Masafumi Minamisawa, Akira Nakamura
Journal: Endoscopy (2024)

Endoscopic retrograde cholangiopancreatography (ERCP)-guided extraction is the gold standard for biliary stone management. However, cystic duct confluence (CDC) stones pose significant challenges due to their unique anatomical and stone characteristics, with a lack of consensus on the optimal therapeutic approach [1] [2]. The issue is further compounded in cystic-dilated CDC spaces, in which stones are prone to escaping the retrieval catheter. Cholangioscopy-assisted lithotripsy is a promising technique that facilitates complex stone management through direct visual stone fragmentation [3]. Featuring a helical 8-wire design with a narrower interwire space at its tip and rotational capability, the novel basket (RASEN2; KANEKA Medix, Tokyo, Japan) has shown superior stone clearance versus conventional baskets in an experimental ex vivo setting [4]. We describe an integrated approach using cholangioscopy-assisted lithotripsy and RASEN2 for CDC stone removal.
One-step technique for endoscopic ultrasound-guided hepaticogastrostomy using a partially covered metal stent for superficial bile duct access
Authors: Takeshi Ogura, Yuki Uba, Nobuhiro Hattori, Kimi Bessho, Hiroki Nishikawa
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is clinically useful as an alternative biliary drainage technique for patients with failed endoscopic retrograde cholangiopancreatography (ERCP) [1]; however, one of the adverse events is biliary peritonitis due to bile leakage during the EUS-HGS procedure. Although biliary peritonitis is usually treated conservatively, it can worsen a patient's condition by delaying oral intake or causing fever postoperatively [2].
Deep invasive mucinous adenocarcinoma without surface amorphous pattern on inflammatory bowel disease: specific disease with specific characterization
Authors: Elena De Cristofaro, Clara Yzet, Louis-Jean Masgnaux, Jean Grimaldi, Jérôme Rivory, Tanguy Fenouil, Mathieu Pioche
Journal: Endoscopy (2024)

Endoscopic characterization of deep invasive carcinoma using current classifications (CONECCT III, JNET III, NICE III) is effective but was not developed for neoplasias associated with inflammatory bowel diseases (IBDs). In IBD, dysplastic lesions often present as flat, non-granular laterally spreading tumors (LST-NGs) [1] [2]. However, mucosal distortion caused by chronic inflammation and regenerative changes can conceal dysplasia, making the detection and characterization of the colonic lesions challenging [3] [4]. The present case illustrates that deep invasive adenocarcinoma can occur with very slight mucosal changes in an IBD lesion ([Video 1]).
Delayed-onset biliary peritonitis after endoscopic ultrasound-guided hepaticogastrostomy for malignant distal biliary obstruction
Authors: Hiroki Sakamoto, Hirotoshi Ishiwatari, Takuya Doi, Junya Sato, Hiroyuki Ono
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is performed when biliary drainage using endoscopic retrograde cholangiopancreatography (ERCP) is difficult [1] [2] [3] [4]. Biliary peritonitis is an adverse event that can be fatal; however, it typically develops immediately after the procedure [5]. Metallic stents reduce the risk of peritonitis. However, plastic stents are preferred for patients with benign diseases or who are surgical candidates. Herein, we present a case of peritonitis that developed 6 days after EUS-BD ([Video 1]).
Appendiceal fecalith misdiagnosed as cecal stromal tumor: don't fall into the trap
Authors: Jinghao Li, Dan Liu, Deliang Li, Yangyang Zhou, Yue Zhao, Bingrong Liu
Journal: Endoscopy (2024)

A 30-year-old man presented with a 2-day history of hematochezia and a 4-year history of intermittent abdominal pain. Computed tomography scan revealed a low-density mass with central calcification in the cecum ([Fig. 1] a). Colonoscopy showed a 15×15 mm cecal mass with a superficial ulcer ([Fig. 1] b). A cecal submucosal tumor was considered. The surgeon recommended ileocecectomy or partial cecectomy. The patient was afraid of surgery and was transferred to our department.
The characteristic “alveolus nest sign” in solid pseudopapillary neoplasm of the pancreas
Authors: Weigang Gu, Justin Ryan L. Tan, Hang Bin Jin, Quifeng Lou, Ka Shing Cheung, Jianfeng Yang, Xiaofeng Zhang
Journal: Endoscopy (2024)

A 23-year-old woman presented with a 1-week history of abdominal pain radiating to the back. The pain was not relieved by proton pump inhibitors. Contrast-enhanced abdominal computed tomography scan demonstrated a round, well-defined, hypodense lesion within the pancreatic body ([Fig. 1]). On endoscopic ultrasound (EUS) elastography there was a 2 × 2.5-cm hypoechoic mass that was predominantly hard (blue) with dispersed heterogeneous soft (green) areas ([Fig. 2]). Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) revealed hyperechoic solid granular components interspersed with small anechoic regions within the pancreatic mass ([Fig. 3]). These characteristics were typical of the "alveolus nest sign" and were present during the arterial and venous phases of CH-EUS ([Video 1]). EUS-guided fine-needle biopsy with subsequent histopathologic examination ([Fig. 4]) and immunohistochemical analysis ([Fig. 5]) yielded a definitive diagnosis of solid pseudopapillary neoplasm (SPN). The patient underwent distal pancreatectomy for definitive treatment.