Understanding immune microenvironment alterations in the brain to improve the diagnosis and treatment of diverse brain diseases.

Abnormal inflammatory states in the brain are associated with a variety of brain diseases. The dynamic changes in the number and function of immune cells in cerebrospinal fluid (CSF) are advantageous for the early prediction and diagnosis of immune diseases affecting the brain. The aggregated factors and cells in inflamed CSF may represent candidate targets for therapy. The physiological barriers in the brain, such as the blood‒brain barrier (BBB), establish a stable environment for the distribution of resident immune cells. However, the underlying mechanism by which peripheral immune cells migrate into the brain and their role in maintaining immune homeostasis in CSF are still unclear. To advance our understanding of the causal link between brain diseases and immune cell status, we investigated the characteristics of immune cell changes in CSF and the molecular mechanisms involved in common brain diseases. Furthermore, we summarized the diagnostic and treatment methods for brain diseases in which immune cells and related cytokines in CSF are used as targets. Further investigations of the new immune cell subtypes and their contributions to the development of brain diseases are needed to improve diagnostic specificity and therapy.

Liquid-based biomarkers in breast cancer: looking beyond the blood.

In recent decades, using circulating tumor cell (CTC), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), exosomes and etc. as liquid biomarkers has received enormous attention in various tumors, including breast cancer (BC). To date, efforts in the area of liquid biopsy predominantly focus on the analysis of blood-based markers. It is worth noting that the identifications of markers from non-blood sources provide unique advantages beyond the blood and these alternative sources may be of great significance in offering supplementary information in certain settings. Here, we outline the latest advances in the analysis of non-blood biomarkers, predominantly including urine, saliva, cerebrospinal fluid, pleural fluid, stool and etc. The unique advantages of such testings, their current limitations and the appropriate use of non-blood assays and blood assays in different settings are further discussed. Finally, we propose to highlight the challenges of these alternative assays from basic to clinical implementation and explore the areas where more investigations are warranted to elucidate its potential utility.

Identification of potential therapeutic targets in urothelial bladder carcinoma of Chinese population by targeted next-generation sequencing.

Patients with urothelial carcinoma (UC) of the bladder have a high risk of death in China. However, a lack of comprehensive molecular profiling in Chinese Han population hinders the development of targeted therapies for bladder cancer. In our present study, we collected fresh bladder tumors from low-grade (T1, N0, M0, G1) non-muscle invasive bladder cancer (NMIBC) patients (n = 16) and high-grade (T2-4, N0, M0, Gx) muscle-invasive bladder cancer (MIBC) patients (n = 16) with their paired normal bladder tissues, and subjected the total genomic DNAs to targeted next-generation sequencing (NGS) for 94 cancer-associated genes. NGS results showed that 30.9% of detected genes (29/94) was mutated in 32 urothelial carcinoma bladder tissues. Furthermore, our results and ICGC database showed that FGFR3, KMT2D, TP53, KDM6A, and ARID1A were the most frequently mutated genes in UC patients. Of note, NMIBC and MIBC displayed distinguishable genomic alterations. FGFR3, KMT2D, AKT1, ARID1A, and STAG2 were the most frequently mutated genes in NMIBC patients, whereas mutations of TP53, CREBBP, FGFR3, KDM6A, KMT2D, and ARID1A were frequently detected in MIBC. Intriguingly, gene ontology and clustering analysis revealed that these frequently mutated genes were highly enriched in signaling pathways responsible for cancer development. Taken together, the mutation frequency of genes associated with UC development in NMIBC and MIBC was screened out in Chinese Han population and elucidation of the related mechanisms provides theoretical basis and technical support for the development of early diagnosis and therapeutic strategies in UC.

Molecular Mechanism of Resistance to Chemotherapy in Gastric Cancers, the Role of Autophagy.

Gastric cancer (GC) is biologically and genetically heterogeneous with complex carcinogenesis at the molecular level. Despite the application of multiple approaches in the GC treatment, its 5-year survival is poor. A major limitation of anti-cancer drugs application is intrinsic or acquired resistance, especially to chemotherapeutical agents. It is known that the effectiveness of chemotherapy remains debatable and varies according to the molecular type of GC. Chemotherapy has an established role in the management of GC. Perioperative chemotherapy or postoperative chemotherapy is applied for localized ones. Most of the advanced GC patients have a poor response to treatment and unfavorable outcomes with standard therapies. Resistance substantially limits the depth and duration of clinical responses to targeted anticancer therapies. Through the use of complementary experimental approaches, investigators have revealed that cancer cells can achieve resistance through adaptation or selection driven by specific genetic, epigenetic, or microenvironmental alterations. Ultimately, these diverse alterations often lead to the activation of MAPK, AKT/mTOR, and Wnt/ß-catenin signaling pathways that, when co-opted, enable cancer cells to survive drug treatments. We have summarized the mechanisms of resistance development to cisplatin, 5-fluorouracil, and multidrug resistance in the GC management. The complexity of molecular targets and components of signaling cascades altered in the resistance development results in the absence of significant benefits in GC treatment, and its efficacy remains low. The universal process responsible for the failure in the multimodal approach in GC treatment is autophagy. Its dual role in oncogenesis is the most unexplored issue. We have discussed the possible mechanism of autophagy regulation upon the action of endogenous factors and drugs. The experimental data obtained in the cultured GC cells need further verification. To overcome the cancer resistance and to prevent autophagy as the main reason of ineffective treatment, it is suggested the concept of the direct influence of autophagy molecular markers followed by the standard chemotherapy. Dozen of studies have focused on finding the rationale for the benefits of such complex therapy. The perspectives in the molecular-based management of GC are associated with the development of molecular markers predicting the protective autophagy initiation and search for novel targets of effective anticancer therapy.

Recent progress in LyP-1-based strategies for targeted imaging and therapy.

The identification of markers expressed by pathological cells or their microenvironment would help to distinguish such cells from the normal tissues. The strategies derived from this theory can be a promising modality for imaging and treating diseases. LyP-1, a tumor homing peptide, can selectively bind to its receptor p32 protein overexpressed in various tumor-associated cells and atherosclerotic plaque macrophages. During recent decades, multiple types of LyP-1-based imaging probes and drug delivery systems have been designed and developed for diagnostic and therapeutic applications. This review first introduces LyP-1 and its receptor p32, as well as its homing, internalization and proapoptotic properties. Next, we highlight recent studies focusing on the applications of LyP-1-based strategies in the diagnosis and treatment of tumors, metastatic lesions, and atherosclerotic plaques. Finally, several limitations in the clinical translation of LyP-1-based bioconjugates are summarized.

Amygdalin-Functionalized Carbon Quantum Dots for Probing ß-Glucosidase Activity for Cancer Diagnosis and Therapeutics.

A fluorescence active nanosystem capable of targeting specific receptors of cancer cells with or without a biorecognition element is advantageous for biosensor studies. Herein, a naturally occurring anticancer drug, amygdalin (synthetic form: Laetrile, a misnomer: vitamin B17), has been modified on the surface of carbon quantum dots, prepared by a hydrothermal method, to probe ß-glucosidase activity. Despite its cyanide toxicity, amygdalin is recently revived to be an anticancer molecule, and the risk factor can be optimized by understanding its binding efficiency with ß-glucosidase in the cancer cells. In this study, an in vitro biorecognition pattern of amygdalin-functionalized carbon quantum dots (Amy@CQDs) toward ß-glucosidase is typically evaluated by an aggregation-induced fluorescence emission mechanism. The optical functionality and structural integrity of CQDs before and after functionalization with amygdalin are comprehensively studied by spectroscopic and microscopic techniques. Our results demonstrate that Amy@CQDs is a stable hydrophilic graphitic carbon nanostructure exhibiting selective fluorescence quenching upon interaction with ß-glucosidase, enabling the lowest detection limit of 134 nM. Hydrolysis products of amygdalin mediated by ß-glucosidase were further confirmed by HPLC and colorimetric methods, indicating the selective binding of the prepared Amy@CQDs, which may find a useful application in cancer diagnosis and therapeutics.

[PIK3CA-related overgrowth syndrome (PROS)]. / Syndromes hypertrophiques secondaires aux mutations de PIK3CA.

This review presents an overview of a recently characterized spectrum of overgrowth syndrome: phosphoinositide-3 kinase (PI3K)-related overgrowth spectrum (PROS). This spectrum encompasses overgrowth syndromes associated with somatic mosaic activating PIK3CA mutations such as megalencephaly-capillary malformation (MCAP) syndrome, dysplatic megalencephaly (DMEG), congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies (CLOVES) syndrome, hemihyperplasia-multiple lipomatosis (HHML), fibroadipose overgrowth and Klippel-Trenaunay syndrome. Mosaic gain of function mutation in PIK3CA gene leads to abnormal AKT-mTOR pathway activation and is responsible of the clinical manifestations. Here, we summarize the current knowledge on this disorder.

El embarazo ectópico se incrementa en el mundo / The ectopic pregnancy is increasing at world level

Se realizó una amplia revisión bibliográfica, que incluyó los trabajos de unos 50 autores nacionales e internacionales obtenidos de libros impresos y de una acuciosa búsqueda en Internet, con el objetivo de evaluar las causas de la elevada incidencia del embarazo ectópico (EE) en su forma clínica complicada. Igualmente indagar sobre sus elementos histórico-epidemiológicos y clasificar el EE; profundizar sobre su fisiopatología, así como diagnosticarlo y manejarlo terapéuticamente. Se realizó la recopilación de datos que permiten alertar a los médicos de la atención primaria y/o especialistas de Ginecoobstetricia, cuándo sospechar la presencia de un embarazo ectópico y poder hacer el diagnóstico antes de que ocurra su complicación. Esto pudiera redundar en la disminución de la elevada mortalidad que se asocia a esta entidad

A wide bibliographic review was made including all papers from 50 national and foreign authors obtained of printed books and of deep search in Internet to assess the causes of the high incidence of ectopic pregnancy (EP) in its complicated clinical presentation, to inquire into on its historical-epidemiological elements and to classify the EP, to deepen on the data collection allowing us to alert to primary care physicians and/or Gynecology and Obstetrics specialist when they must to suspect on the presence of an ectopic pregnancy and to made the diagnosis before appearance of a complication. It could to have an effect on decrease of the high mortality associated with this entity

El embarazo ectópico se incrementa en el mundo / The ectopic pregnancy is increasing at world level

Se realizó una amplia revisión bibliográfica, que incluyó los trabajos de unos 50 autores nacionales e internacionales obtenidos de libros impresos y de una acuciosa búsqueda en Internet, con el objetivo de evaluar las causas de la elevada incidencia del embarazo ectópico (EE) en su forma clínica complicada. Igualmente indagar sobre sus elementos histórico-epidemiológicos y clasificar el EE; profundizar sobre su fisiopatología, así como diagnosticarlo y manejarlo terapéuticamente. Se realizó la recopilación de datos que permiten alertar a los médicos de la atención primaria y/o especialistas de Ginecoobstetricia, cuándo sospechar la presencia de un embarazo ectópico y poder hacer el diagnóstico antes de que ocurra su complicación. Esto pudiera redundar en la disminución de la elevada mortalidad que se asocia a esta entidad (AU)

A wide bibliographic review was made including all papers from 50 national and foreign authors obtained of printed books and of deep search in Internet to assess the causes of the high incidence of ectopic pregnancy (EP) in its complicated clinical presentation, to inquire into on its historical-epidemiological elements and to classify the EP, to deepen on the data collection allowing us to alert to primary care physicians and/or Gynecology and Obstetrics specialist when they must to suspect on the presence of an ectopic pregnancy and to made the diagnosis before appearance of a complication. It could to have an effect on decrease of the high mortality associated with this entity (AU)

El embarazo ectópico se incrementa en el mundo / The ectopic pregnancy is increasing at world level

Se realizó una amplia revisión bibliográfica, que incluyó los trabajos de unos 50 autores nacionales e internacionales obtenidos de libros impresos y de una acuciosa búsqueda en Internet, con el objetivo de evaluar las causas de la elevada incidencia del embarazo ectópico (EE) en su forma clínica complicada. Igualmente indagar sobre sus elementos histórico-epidemiológicos y clasificar el EE; profundizar sobre su fisiopatología, así como diagnosticarlo y manejarlo terapéuticamente. Se realizó la recopilación de datos que permiten alertar a los médicos de la atención primaria y/o especialistas de Ginecoobstetricia, cuándo sospechar la presencia de un embarazo ectópico y poder hacer el diagnóstico antes de que ocurra su complicación. Esto pudiera redundar en la disminución de la elevada mortalidad que se asocia a esta entidad (AU)

A wide bibliographic review was made including all papers from 50 national and foreign authors obtained of printed books and of deep search in Internet to assess the causes of the high incidence of ectopic pregnancy (EP) in its complicated clinical presentation, to inquire into on its historical-epidemiological elements and to classify the EP, to deepen on the data collection allowing us to alert to primary care physicians and/or Gynecology and Obstetrics specialist when they must to suspect on the presence of an ectopic pregnancy and to made the diagnosis before appearance of a complication. It could to have an effect on decrease of the high mortality associated with this entity (AU)