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941
Case Report Open Access
Xiaoting Song, Ran Wang, Yiyan Zhang, Wei Li, Jing Qiu, Liang Liu, Zhongchao Wang, Yang Li, Xingshun Qi
Published online October 26, 2022
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2022.00105
Abstract
There is a risk of post-polypectomy bleeding (PPB) in patients undergoing a colonoscopic polypectomy, especially in those taking warfarin. Undoubtedly, the use of warfarin can raise [...] Read more.

There is a risk of post-polypectomy bleeding (PPB) in patients undergoing a colonoscopic polypectomy, especially in those taking warfarin. Undoubtedly, the use of warfarin can raise the risk of bleeding, but its withdrawal increases the risk of thrombosis. Therefore, the management of warfarin during a colonoscopic polypectomy is particularly important to balance the risk of thrombosis and bleeding. Herein, we reported a case taking warfarin due to mitral and aortic valve replacement who developed cerebral infarction and congestive heart failure (CHF) after a colonoscopic polypectomy. Knowledge regarding management of warfarin and heparin bridging was reviewed to guide clinical interventions about how to avoid thrombotic and bleeding events.

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942
Original Article Open Access
Zhigang Liu, Sizheng Li, Yahao Ling, Haiyan Jiang, Lian Kuang, Jie Bao, Jing Li, Peicheng Zhang, Hongtao Jin
Published online October 26, 2022
Future Integrative Medicine. doi:10.14218/FIM.2022.00030
Abstract
The mechanism underlying lung injury due to atmospheric fine particulate matter (PM2.5) remains unclear, and currently, there are no medications for specific intervention. Different [...] Read more.

The mechanism underlying lung injury due to atmospheric fine particulate matter (PM2.5) remains unclear, and currently, there are no medications for specific intervention.

Different doses of grape skin extract (GSE, 0.1, 0.2, and 0.4 g/kg, respectively) were administered prophylactically to the treatment groups, while sterile water was administered to the control and model groups. PM2.5 in suspension (1 mL at 30 mg/kg) was administered twice weekly for six weeks. The rats were sacrificed 48 h after the last administration. Pulmonary function was assessed weekly by a whole-body plethysmography system. Hematoxylin-eosin staining, alveolar lavage fluid leukocyte classification and counts, detection of cytokines with an enzyme-linked immunosorbent assay, and other methods were employed to evaluate pathological changes and inflammation of the lungs, amino acid metabolomics, and lipid metabolomics. A gene chip was used for mRNA profiling to identify potential drug targets.

Lung function was diminished compared to the control group. Pathological changes were significant, and lung inflammation was more evident in the model group. There were also apparent changes in lung tissues and serum metabolites of amino acids and lipids. The lung function, the inflammatory response, fibrosis, and the number of phagocytes of the lung interstitium were significantly improved with GSE treatment. Local inflammation of lung tissue was reduced. Serum, lung tissue amino acids, and lipid metabolites underwent dramatic corrections. Functional enrichment analysis found that GSE improved the lung damage caused by PM2.5 via the complement and oxidative phosphorylation pathways.

GSE significantly improved lung injury and pulmonary inflammation induced by PM2.5 in rats. The detection results of multiple omics provided important information for subsequent comprehensive clarification of potential targets and intervention mechanisms of GSE.

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943
Review Article Open Access
Graziele Silva Paz, Janaina Fernandes
Published online October 25, 2022
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2022.00032
Abstract
The intestinal microbiota is considered a large organ in the human body performing functions in the host that range from supporting digestion and absorption of nutrients from the [...] Read more.

The intestinal microbiota is considered a large organ in the human body performing functions in the host that range from supporting digestion and absorption of nutrients from the diet to regulating the various processes in the host. Maintaining a diverse and stable microbiota is critical to maintaining host homeostasis and health. Studies have suggested the relationship between the microbial changes and the development of several pathologies. In this context, metformin, has shown to be a promising drug for the regulation of the microbiota, thus favoring the prevention and treatment of type 2 diabetes mellitus (T2DM), obesity, cancer, the inflammatory state of human immunodeficiency virus (HIV), heart disease, Alzheimer’s disease and aging, and pathologies associated with dysbiosis. In this review, the main aspects on the importance of metformin’s action on dysbiosis, and the factors that regulate the metformin uptake and activity as genetic polymorphisms and GLP-1 receptor activation were discussed.

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944
Original Article Open Access
Sylvain Nsangou Pechangou, Brice Edie Enang, Vigny Sayal Ngohoba, Emmanuel Mfotie Njoya, Frederic Nico Njayou, Paul Fewou Moundipa
Published online October 24, 2022
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2022.00039
Abstract
Codiaeum variegatum (C. variegatum), which is commonly known as garden croton, is a medicinal plant used for the treatment of amoebiasis in Cameroon and some Asian countries. The [...] Read more.

Codiaeum variegatum (C. variegatum), which is commonly known as garden croton, is a medicinal plant used for the treatment of amoebiasis in Cameroon and some Asian countries. The present study aims to evaluate the antioxidant and anti-inflammatory activities of the stem crude extracts of C. variegatum.

Aqueous, hydroethanolic 70/30 (v/v) and ethanolic extracts (EE) were tested for antioxidant activity using 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging, ferric iron-reducing antioxidant power (FRAP), and lipid peroxidation inhibitory assays. The anti-inflammatory activity was determined based on the inhibition of nitric oxide (NO) production on isolated mouse macrophages activated by Saccharomyces cerevisiae. Furthermore, the inhibitory effect of these extracts on 5-lipoxygenase activity and bovine serum albumin (BSA) denaturation was determined, and the activation of two lysosomal enzymes involved in phagocytosis was performed. The phytochemical screening of the plant extracts was performed using standard methods for phenol, flavonoid, tannin, etc.

The results revealed that the EE exhibited the highest antioxidant activity, in terms of DPPH-free radical scavenging activity, FRAP, and its potential to inhibit lipid peroxidation (IC50 = 77.04 µg extract/mol of DPPH; EC50 = 543.6 µg/mL and IC50 = 21.52 µg/mL, respectively). However, this activity remained significantly lower than that of ascorbic acid (p < 0,05). Furthermore, the hydroethanolic extract (HE) had the highest anti-inflammatory activity on isolated mouse macrophages, in terms of inhibitory activity on NO production, BSA denaturation, and 5-lipoxygenase activity (IC50 = 8.80 µg/mL, IC50 = 205.9 µg/mL, IC50 = 0.08 µg/mL, respectively). However, there was no significant difference in the inhibitory activity of baicalin. Moreover, the activity of acid phosphatase and alkaline phosphatase increased in the presence of the HE (EC50 = 10.03 µg/mL and EC50 = 0.274 µg/mL, respectively). The phytochemical analysis of these extracts indicates the presence of phenolic compounds, and these may be responsible for the observed activities.

Overall, these results demonstrate that the hydroethanolic and ethanolic stem extracts of C. variegatum have good antioxidant and anti-inflammatory potential.

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945
Original Article Open Access
Xukuo Liu, Jianing Zhao, Jiao Liu, Huanfang Fan, Na Guo, Zhihua Du, Haina Wu, Dehui Li
Published online October 24, 2022
Future Integrative Medicine. doi:10.14218/FIM.2022.00031
Abstract
Chemotherapy-induced nausea and vomiting (CINV) are both common clinical problems in cancer patients. As a traditional Chinese medicine treatment method, acupuncture has a remarkable [...] Read more.

Chemotherapy-induced nausea and vomiting (CINV) are both common clinical problems in cancer patients. As a traditional Chinese medicine treatment method, acupuncture has a remarkable healing effect on the treatment of nausea and vomiting, but a systematic meta-analysis is lacking concerning this topic.

This paper searched the randomized controlled clinical trial literature on acupuncture for the prevention of CINV in the Pubmed, EMBASE, CNKI, WF (WAFANG DATE), Cochrane, and VIP (CQVIP) databases with a search date of October 20, 2021. An independent quality evaluation and effect size extraction of the literature were performed by two researchers, and the meta-analysis and quality evaluation of all the literature was performed using RevMan 5.4. A total of 18 publications meeting the criteria were screened for the meta-analysis with a total of 1,135 patients.

Combined acupuncture prophylaxis was significantly better than other chemotherapy regimens in comparison with conventional chemotherapy regimens (risk ratio (RR) = 1.29; 95% confidence interval (CI): 1.17–1.43, p < 0.00001; odds ratio (OR) = 3.61; 95% CI: 2.19–5.96, p < 0.00001). Combined acupuncture was also effective in the prevention of side effects, such as loss of appetite (RR = 0.64; 95% CI:0.42–0.97, p < 0.00001; OR = 0.52; 95% CI:0.28–0.96, p = 0.04), constipation (RR = 0.57; 95% CI :0.44–0.73, p < 0.00001; OR = 0.30; 95% CI:0.18–0.51, p < 0.00001), and diarrhea (RR = 0.58; 95% CI:0.39–0.86, p < 0.00001; OR = 0.31; 95% CI:0.13–0.72, p < 0.00001).

Acupuncture prevention could reduce the incidence of CINV which has certain research value and thus would be worthy of research trials and clinical application.

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946
Review Article Open Access
Kun-Li Yin, Ming Li, Pei-Pei Song, Yu-Xin Duan, Wen-Tao Ye, Wei Tang, Norihiro Kokudo, Qiang Gao, Rui Liao
Published online October 18, 2022
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2022.00326
Abstract
Hepatic stellate cells (HSCs) play an essential role in various liver diseases, and exosomes are critical mediators of intercellular communication in local and distant microenvironments. [...] Read more.

Hepatic stellate cells (HSCs) play an essential role in various liver diseases, and exosomes are critical mediators of intercellular communication in local and distant microenvironments. Cellular crosstalk between HSCs and surrounding multiple tissue-resident cells promotes or inhibits the activation of HSCs. Substantial evidence has revealed that HSC-derived exosomes are involved in the occurrence and development of liver diseases through the regulation of retinoid metabolism, lipid metabolism, glucose metabolism, protein metabolism, and mitochondrial metabolism. HSC-derived exosomes are underpinned by vehicle molecules, such as mRNAs and microRNAs, that function in, and significantly affect, the processes of various liver diseases, such as acute liver injury, alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, and cancer. As such, numerous exosomes derived from HSCs or HSC-associated exosomes have attracted attention because of their biological roles and translational applications as potential targets for therapeutic targets. Herein, we review the pathophysiological and metabolic processes associated with HSC-derived exosomes, their roles in various liver diseases and their potential clinical application.

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947
Review Article Open Access
Yi-Bo Fu, Gang Yang, Jiang-Dong Qiu, Tai-Ping Zhang
Published online October 18, 2022
Cancer Screening and Prevention. doi:10.14218/CSP.2022.00013
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is most often detected at an advanced stage due to a lack of symptoms at the first stage. PDAC is relatively uncommon, and screening of the [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is most often detected at an advanced stage due to a lack of symptoms at the first stage. PDAC is relatively uncommon, and screening of the asymptomatic population is not feasible or cost-effective. Therefore, screening of individuals in high-risk groups is recommended. Diabetes mellitus (DM) is associated with PDAC, and patients with DM are recognized as a high-risk group for PDAC. Here, we review the complex relationship between pancreatic cancer and DM, including the role of diabetes as a risk factor for pancreatic cancer and its role in inducing the destruction of islet β cells and insulin resistance. We also review the current study about discriminating DM with pancreatic cancer from normal DM and the model for early screening of pancreatic cancer in DM.

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948
Original Article Open Access
Ashok Kumar, Avtar Chand Rana, Bharat Parashar, Ankit Kumar, Deepak Kumar Semwal
Published online October 17, 2022
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2022.00047
Abstract
Myrica nagi Thunb., belonging to the family Myricaceae, is used in Indian traditional medicine to treat diarrhea. This study aimed to assess the anti-diarrheal activity of the aqueous [...] Read more.

Myrica nagi Thunb., belonging to the family Myricaceae, is used in Indian traditional medicine to treat diarrhea. This study aimed to assess the anti-diarrheal activity of the aqueous extract of stem bark of Myrica nagi (AEMN) using castor oil-induced diarrhea and charcoal meal tests in albino rats.

Wistar rats of either sex were divided into five groups (n = 6). In castor oil-induced diarrhea, castor oil (10 mL/kg p.o.) was used as an inducer, and loperamide (3 mg/kg p.o.) was used as the standard drug. However, in charcoal-induced diarrhea, atropine sulphate (5 mg/kg p.o.) was used as a standard drug. AEMN was administered to rats at 125, 250, and 500 mg/kg p.o., respectively. These rats were monitored for 4 h and the first defecation time was noted. The fecal matter was collected every 30 min and its frequency and weight were measured. Charcoal meal test was performed on the rats.

AEMN in different doses significantly reduced the first fecal output, the cumulative number of feces, and the cumulative weight of feces after four hours in the castor oil-induced diarrheal model compared with the control group. The extract at 250 mg/kg p.o. and 500 mg/kg also significantly (p < 0.001) reduced the distance travelled by the charcoal.

AMEN alleviates diarrhea and related problems at higher dose i.e. 500 mg/kg. Tannins, flavonoids and terpenoids may be responsible for the antidiarrheal effects.

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949
Letter to the Editor Open Access
Xiangyang Li, Tianhang Li
Published online October 9, 2022
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2022.00062
950
Opinion Open Access
Andrew W. Taylor-Robinson, Thanh H. Nguyen
Published online October 9, 2022
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2022.00089
951
Review Article Open Access
Daniel Hokinson, Astia Sanjaya, Juandy Jo
Published online October 9, 2022
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2022.00092
Abstract
The world has witnessed increased incidences of severe acute hepatitis in children since early 2021, in which the total number of global cases was over 1,000 in July 2022. Those [...] Read more.

The world has witnessed increased incidences of severe acute hepatitis in children since early 2021, in which the total number of global cases was over 1,000 in July 2022. Those cases of severe acute hepatitis were intriguing, as they were not caused by the common hepatitis A-E viruses. Additionally, the cause remains unknown to date, thus named as severe acute hepatitis of unknown etiology. The World Health Organization, supported by regional and national health agencies, has issued the working case definitions in order to closely monitor the development of this disease worldwide. As one of its member states, Indonesia has also adopted the case definitions and subsequently issued a health decree to increase public awareness and to conduct an early surveillance on this illness. It remains to be seen whether this updated public health policy would be successful to control the numbers of cases of severe acute hepatitis of unknown etiology in Indonesia.

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952
Short Communication Open Access
Yee Hui Yeo, Xinyuan He, Fan Lv, Yunyu Zhao, Yi Liu, Ju Dong Yang, Jian Zu, Fanpu Ji, Mindie H. Nguyen
Published online September 30, 2022
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2022.00313
Abstract
Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide dataset that [...] Read more.

Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide dataset that includes more than 99% of the decedents in the U.S. between April 2012 and September 2021 was used. Projected age-standardized mortality during the pandemic were estimated according to prepandemic mortality rates, stratified by season. Excess deaths were determined by estimating the difference between observed and projected mortality rates. A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included. Following an increasing trend of cirrhosis-related mortality before the pandemic, with a semiannual percentage change (SAPC) of 0.54% [95% confidence interval (CI): (0.0–1.0%), p=0.036], a precipitous increase with seasonal variation occurred during the pandemic (SAPC 5.35, 95% CI: 1.9–8.9, p=0.005). Significantly increased mortality rates were observed in those with alcohol-associated liver disease (ALD), with a SAPC of 8.44 (95% CI: 4.3–12.8, p=0.001) during the pandemic. All-cause mortality of nonalcoholic fatty liver disease rose steadily across the entire study period with a SAPC of 6.79 (95% CI: 6.3–7.3, p<0.001). The decreasing trend of HCV-related mortality was reversed during the pandemic, while there was no significant change in HBV-related deaths. While there was significant increase in COVID-19-related deaths, more than 55% of the excess deaths were the indirect impact of the pandemic. We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD, with evidence in both direct and indirect impact. Our findings have implications on formulating policies for patients with cirrhosis.

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953
Corrigendum Open Access
954
Original Article Open Access
Sandrine Charles, Ophelia Gestin, Jérémie Bruset, Dominique Lamonica, Virgile Baudrot, Arnaud Chaumot, Olivier Geffard, Thomas Lacoue-Labarthe, Christelle Lopes
Published online September 29, 2022
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2022.00043
Abstract
Increasing confidence in using in vitro and in silico model-based data to aid the chemical risk assessment process is one of the most significant challenges faced by regulatory [...] Read more.

Increasing confidence in using in vitro and in silico model-based data to aid the chemical risk assessment process is one of the most significant challenges faced by regulatory authorities. A crucial concern is taking full advantage of scientifically valid physiologically-based kinetic (PBK) models. The present study aims to present a very innovative solution of a fully generic PBK model written as a set of ordinary differential equations (ODE).

This study proposes an innovative and unified modeling framework for writing PBK equations as matrix ODE and their solutions, expressed with matrix products. This generic PBK solution considers as many state variables as needed to quantify chemical absorption, distribution, metabolism, and excretion processes within living organisms when exposed to chemical substances.

We first introduce our PBK modeling framework, with all the intermediate steps from the matrix ODE to the exact solution. Then we apply this framework to bioaccumulation testing before illustrating its concrete use through complementary case studies regarding species, compounds, and model complexity.

This generic PBK model makes it possible for any compartmentalization to be considered, as well as all appropriate interconnections between compartments and with the external medium.

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955
Review Article Open Access
Matthew Goldman, Brandon Lucke-Wold, Jason Katz, Bavly Dawoud, Abeer Dagra
Published online September 28, 2022
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2022.00081
Abstract
Traumatic brain injuries (TBI), ischemic stroke, hemorrhagic stroke, brain tumors, and seizures have diverse and sometimes overlapping associated breathing patterns. Homeostatic [...] Read more.

Traumatic brain injuries (TBI), ischemic stroke, hemorrhagic stroke, brain tumors, and seizures have diverse and sometimes overlapping associated breathing patterns. Homeostatic mechanisms for respiratory control are intertwined with complex neurocircuitry, both centrally and peripherally. This paper summarizes the neurorespiratory control and pathophysiology of its disruption. It also reviews the clinical presentation, ventilatory management, and emerging therapeutics. This review additionally serves to update all recent preclinical and clinical research regarding the spectrum of respiratory dysfunction. Having a solid pathophysiological foundation of disruptive mechanisms would permit further therapeutic development. This novel review bridges experimental/physiological data with bedside management, thus allowing neurosurgeons and intensivists alike to rapidly diagnose and treat respiratory sequelae of acute brain injury.

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956
Review Article Open Access
Binxin Cui, Wanting Yang, Gaoyue Guo, Xiaofei Fan, Xiaoyu Wang, Yangyang Hui, Sipu Wang, Kui Jiang, Wentian Liu, Junling Liu, Chao Sun
Published online September 28, 2022
Gene Expression. doi:10.14218/GEJLR.2022.00003
Abstract
The liver contributes substantially to the metabolic transformation and transport of lipids and lipoproteins. These bioactive substances represent a heterogeneous group of molecules [...] Read more.

The liver contributes substantially to the metabolic transformation and transport of lipids and lipoproteins. These bioactive substances represent a heterogeneous group of molecules with pivotal roles in diverse pathological processes as well as disease progression, the advent of complications, and the response to specific treatments in the context of cirrhosis. The present mini-review aims to summarize the underlying mechanisms regarding lipid changes across divergent circumstances. Recent evidence suggests the prognostic value of lipids/lipoproteins and their close relationship to an increased risk mortality among cirrhotic patients. However, more research regarding the development of risk stratification and therapeutic strategies based on altered lipid profiles in patients with cirrhosis is warranted.

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957
Review Article Open Access
Wegahta Weldemichael, Dongwei Zhang, Jingmei Lin
Published online September 28, 2022
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2022.00021
Abstract
The pathomorphological features of primary biliary cholangitis (PBC) is well-established. However, the distinction between PBC recurrence, and T cell-mediated rejection or chronic [...] Read more.

The pathomorphological features of primary biliary cholangitis (PBC) is well-established. However, the distinction between PBC recurrence, and T cell-mediated rejection or chronic rejection remains as a challenge for pathologists. Due to the overlapping morphology, correct diagnosis requires a highly specific discrimination. Accurate diagnosis plays an essential role in patient management since different therapeutic strategies are used. This review focused on the role of pathologists in evaluating the allograft liver biopsy of patients with PBC as the leading cause of native liver cirrhosis. Furthermore, the clinicopathologic features of recurrent PBC, and T cell-mediated rejection or chronic rejection were discussed in detail, with emphasis in distinguishing the histopathology, morphologic variant, and diagnostic pitfalls.

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958
Editorial Open Access
Feng Yin, Huamin Wang
Published online September 28, 2022
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2022.00025
959
Announcement Open Access
The Editorial Office of Gene Expression
Published online September 28, 2022
Gene Expression. doi:10.14218/GEJLR.2022.00000
960
Opinion Open Access
Victor C. Kok
Published online September 28, 2022
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2022.00087
Abstract
Recently, an anti-trophoblast surface antigen-2 (Trop-2) antibody-drug conjugate targeting Trop-2 positive cancer cells has been approved for treating patients with unresectable [...] Read more.

Recently, an anti-trophoblast surface antigen-2 (Trop-2) antibody-drug conjugate targeting Trop-2 positive cancer cells has been approved for treating patients with unresectable locally advanced or metastatic triple-negative breast cancer, who have failed two or more lines of systemic chemotherapy. This has renewed the interest in translational research of Trop-2 positive breast cancer, the gene TACSTD2 and microRNAs that interact with it, and the signaling networks sparked by Trop-2 mediated signaling. In addition, this opinion paper argues that exosomes, extracellular vesicles that are released from Trop-2 positive cancer cells, could play a significant role in cancer progression. Furthermore, diagnostic applications using Trop-2-released exosomes, the cargo exosomes carry, which could be any genetic information such as specific miRNAs, adhesion molecules such as integrins, and metabolites, are yet to be explored in breast cancer patients. Most of the evidence and data are obtained from studies in epithelial cancers other than breast cancers, which have been introduced in the current paper. Therefore, this article briefly summarizes previously published data on other cancer types, forms some hypotheses, and proposes research questions and directions that may be explored further.

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