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Prostate cancer (PCa) incidence is increasing and endangers men’s lives. Early detection of PCa could improve overall survival (OS) by preventing metastasis. The prostate-specific antigen (PSA) test is a popular screening method. Several advisory groups, however, warn against using the PSA test due to its high false positive rate, unsupported outcome, and limited benefit. The number of disease-related biopsies performed annually far outweighs the number of diagnoses. Thus, there is an urgent need to develop accurate diagnostic biomarkers to detect PCa and distinguish between aggressive and indolent cancers. Recently, non-coding RNA (ncRNA), circulating tumor DNA (ctDNA)/ctRNA, exosomes, and metabolomic biomarkers in the liquid biopsies (LBs) of patients with PCa showed significant differences and clinical benefits in diagnosis, prognosis, and monitoring response to therapy. The analysis of urinary exosomal ncRNA presented a substantial correlation among Exos-miR-375 downregulation, clinical T stage, and bone metastases of PCa. Furthermore, the expression of miR-532-5p in urine samples was a vital predictive biomarker of PCa progression. Thus, this review focuses on promising molecular and metabolomic biomarkers in LBs from patients with PCa. We thoroughly addressed the most recent clinical findings of LB biomarker use in diagnosing and monitoring PCa in early and advanced stages.

Abstract Background To date, standardising clinical predictive biomarkers for assessing the response to immunotherapy remains challenging due to variations in personal genetic signatures, tumour microenvironment complexities and epigenetic onco‐mechanisms. Main body Early monitoring of key non‐coding RNA (ncRNA) biomarkers may help in predicting the clinical efficacy of cancer immunotherapy and come up with standard predictive ncRNA biomarkers. For instance, reduced miR‐125b‐5p level in the plasma of non‐small cell lung cancer patients treated with anti‐PD‐1 predicts a positive outcome. The level of miR‐153 in the plasma of colorectal cancer patients treated with chimeric antigen receptor T lymphocyte (CAR‐T) cell therapy may indicate the activation of T‐cell killing activity. miR‐148a‐3p and miR‐375 levels may forecast favourable responses to CAR‐T‐cell therapy in B‐cell acute lymphoblastic leukaemia. In cancer patients treated with the GPC3 peptide vaccine, serum levels of miR‐1228‐5p, miR‐193a‐5p and miR‐375‐3p were reported as predictive biomarkers of good response and improved overall survival. Therefore, there is a critical need for further studies to elaborate on the key ncRNA biomarkers that have the potential to predict early clinical responses to immunotherapy. Conclusion This review summarises important predictive ncRNA biomarkers that were reported in cancer patients treated with different immunotherapeutic modalities, including monoclonal antibodies, small molecule inhibitors, cancer vaccines and CAR‐T cells. In addition, a concise discussion on forthcoming perspectives is provided, outlining technical approaches for the optimal utilisation of immunomodulatory ncRNA biomarkers as predictive tools and therapeutic targets.

Abstract Objectives To screen and verify differential genes affecting the prognosis of breast cancer. Methods Breast cancer gene expression datasets were downloaded from the GEO database, and original data were analyzed in R. The TIMER database was used to analyze the relationship between ANLN and UBE2T and immune cell infiltration. Results Ten hub-key genes were identified, and survival analysis showed that UBE2T and ANLN were upregulated in breast cancer and their upregulation was associated with a poor prognosis. ANLN and UBE2T upregulation was associated with the prevalence of Th1 and Th2 cells, shifting the Th1/Th2 balance to Th2 in Basal and Luminal-B breast cancers, which indicates a poor prognosis (P

Summary: Macrophages (MΦs) type 2 (M2) play crucial roles in the pathogenesis of gastrointestinal cancers (GIC) by enhancing tumor progression, invasion, and metastasis. Polarized M2 has been linked to the increase of GIC tumorigenesis and drug resistance. Several studies reported that M2-derived exosomal non-coding RNAs (Exos-ncRNAs) play pivotal roles in the modulation of the GIC tumor microenvironment (TME) and mostly promote drug resistance and immunosuppression. The impact of M2-Exos-ncRNAs is attributed to altered signaling pathways, enhancement of immunoregulatory mechanisms, and post-transcriptional modulation. Recent studies described novel targets in M2-TAMs-derived Exos-ncRNAs and potential promising clinical outcomes such as inhibiting tumor formation, invasion, and metastasis. Highlighting current knowledge of M2-Exos-ncRNAs involved in GIC pathogenesis and immunomodulation would thus be a significant contribution to improving clinical outcomes. In this review, we summarize recent updates on the role of M2-TAMs-Exos-ncRNAs in GIC pathogenesis, immunosuppression, and drug resistance. A deep understanding of M2-TAMs-derived Exos-ncRNAs could help to identify potential biomarkers and therapeutic targets.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is persistently threatening the lives of thousands of individuals globally. It triggers pulmonary oedema, driving to dyspnoea and lung failure. Viral infectivity of coronavirus disease 2019 (COVID‐19) is a genuine challenge due to the mutagenic genome and mysterious immune‐pathophysiology. Early reports highlighted that extracellular vesicles (exosomes, Exos) work to enhance COVID‐19 progression by mediating viral transmission, replication and mutations. Furthermore, recent studies revealed that Exos derived from immune cells play an essential role in the promotion of immune cell exhaustion by transferring regulatory lncRNAs and miRNAs from exhausted cells to the active cells. Fortunately, there are great chances to modulate the immune functions of Exos towards a sustained repression of COVID‐19. Engineered Exos hold promising immunotherapeutic opportunities for remodelling cytotoxic T cells’ function. Immune cell‐derived Exos may trigger a stable epigenetic repression of viral infectivity, restore functional cytokine‐producing T cells and rebalance immune response in severe infections by inducing functional T regulatory cells (Tregs). This review introduces a view on the current outcomes of immunopathology, and immunotherapeutic applications of immune cell‐derived Exos in COVID‐19, besides new perspectives to develop novel patterns of engineered Exos triggering novel anti‐SARS‐CoV‐2 immune responses.

Osteoarthritis (OA) is a serious joint inflammation that leads to cartilage degeneration and joint dysfunction. Mesenchymal stem cells (MSCs) are used as a cell-based therapy that showed promising results in promoting cartilage repair. However, recent studies and clinical trials explored unsatisfied outcomes because of slow chondrogenic differentiation and increased calcification without clear reasons. Here, we report that the overexpression of indoleamine 2,3 dioxygenase 1 (IDO1) in the synovial fluid of OA patients impairs chondrogenic differentiation of MSCs in the joint of the OA mice model. The effect of MSCs mixed with IDO1 inhibitor on the cartilage regeneration was tested compared to MSCs mixed with IDO1 in the OA animal model. Further, the mechanism exploring the effect of IDO1 on chondrogenic differentiation was investigated. Subsequently, miRNA transcriptome sequencing was performed for MSCs cocultured with IDO1, and then TargetScan was used to verify the target of miR-122-5p in the SF-MSCs. Interestingly, we found that MSCs mixed with IDO1 inhibitor showed a significant performance to promote cartilage regeneration in the OA animal model, while MSCs mixed with IDO1 failed to stimulate cartilage regeneration. Importantly, the overexpression of IDO1 showed significant inhibition to Sox9 and Collagen type II (COL2A1) through activating the expression of β-catenin, since inhibiting of IDO1 significantly promoted chondrogenic signaling of MSCs (Sox9, COL2A1, Aggrecan). Further, miRNA transcriptome sequencing of SF-MSCs that treated with IDO1 showed significant downregulation of miR-122-5p which perfectly targets Wnt1. The expression of Wnt1 was noticed high when IDO1 was overexpressed. In summary, our results suggest that IDO1 overexpression in the synovial fluid of OA patients impairs chondrogenic differentiation of MSCs and cartilage regeneration through downregulation of miR-122-5p that activates the Wnt1/β-catenin pathway.

Psychological distress scale is highly recommended for cancer patients’ care. Several psychological scales have been implemented in cancer outpatient clinics. However, the use of the psychological distress scale, particularly distress thermometer (DT), in the inpatient has not been reported. In this study, we report the efficacy of DT in the determination of cancer inpatients’ supporting needs. A total of 170 inpatients diagnosed with cancer have been enrolled in this study. Only 132 patients matched the inclusion criteria, while other cases were excluded because of other diseases associated with cancer. The standardized problem list (PL) and Hospital Anxiety and Depression Scale (HADS) were implemented in comparison with DT. Then, the cut-off score of DT was performed to identify clinically significant differences. The analysis of the receiver operating characteristic (ROC) curve revealed that a DT cut-off score of 4 displayed 0.76 under the ROC curve. Sensitivity showed 0.86 sensitivity for cut-off score 4 and a specificity of 0.56 relative to the HADS cut-off score (≥15). DT scores were found independent of medical variables such as cancer type and stage, recurrence, or metastasis. Clinical ECOG-SP showed a significant association with the DT cut-off score (P ≤ 0.05). Regarding PL, patients with scores above DT cut-off were suffering 21 of 40 problems in all categories. Furthermore, patients that scored above the DT cut-off significantly showed an association with high support needs. DT scale showed significant performance in the evaluation of psychological distress among cancer inpatients through the efficient determination of their support needs.

Background: Chondromyxoid fibroma (CMF) is a very rare case usually appears around the knee. CMF presented high recurrence rate 25% among treated cases. However, in this case, interestingly CMF in the right upper arm was radiologically and pathologically diagnosed. It measures a 6.9 mm × 1.7 mm lesion. Case presentation: 36-year-old male showed CMF in the juxtacortic proximal humerus. Computed tomography (CT) and magnetic resonance imaging (MRI) of the right upper arm interestingly presented an expansile, mildly lobulated, septate lesion a 6.9 mm × 1.7 mm. Pathological analysis of biopsy showed a bony tissue consisting of cartilaginous, fibrous and myxoid stroma with abundant stellate shaped cells that present vary nucleus size and a minority of nuclear division. Surgical allogeneic bone graft and plate internal fixation was performed after the intralesional curettage surgery. Postoperation the patient was received doxorubicin 50–75 mg/m2 21 days cycle. Results showed that the intralesional curettage surgery of CMF, allogeneic bone graft and plate internal fixation combined with doxorubicin was successfully treated CMF and efficiently prevent relapse during 20 months of observations. Conclusion: the juxtacortic CMF was unusually diagnosed in the proximal humerus, it has been efficiently eliminated by a surgical operation and doxorubicin 50–75 mg/m2 that prevented tumor recurrence. Keywords: Chondromyxoid fibroma, Juxtacortic, Proximal humerus, Bone fibroma

Background/Aims: Abnormal glucose metabolism and lipid metabolism are two key issues in Type 1 diabetes mellitus (T1DM). Insulin can control carbohydrate metabolism adequately, but cannot regulate lipid metabolism well in patients with T1DM. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cured type 2 diabetes mellitus in clinical trials and have improved T1DM glycemic control in preclinical studies. However, previous studies have not reported whether GLP-1 can lower the serum concentration of non-esterified fatty acids (NEFAs). In this study, we examine whether GLP-1 can affect serum NEFA levels. Methods: The bioactivity of EGLP-1 (a novel GLP-1 analog) in vitro was analyzed in CG-HEK293 cells and with high-performance liquid chromatography. An intraperitoneal glucose tolerance test (IPGTT) was used to analyze the acute and sustained hypoglycemic effects of EGLP-1 in normal C57BL/6J mice. Streptozotocin-induced hyperglycemic mice were used to study the effects of EGLP-1 on blood glucose and NEFAs as well as its mechanism. Results: EGLP-1 activated GLP-1R and resisted dipeptidyl peptidase-IV digestion in vitro. Additionally, EGLP-1 had an insulinotropic action in vivo that lasted for approximately 6 h. In Streptozotocin-induced hyperglycemic mice, EGLP-1 improved hyperglycemia, inhibited food intake, and increased β-cell area. Serum physiological indexes showed that insulin and C-peptide levels were increased, while NEFA and triacylglycerol concentrations were decreased. Western blot analysis revealed that EGLP-1 significantly reduced phosphorylated-hormone sensitive lipase (pHSL) levels in white adipose tissue. Conclusions: EGLP-1 can improve hyperglycemia by increasing islet β-cell area and improving β-cell function, possibly due to reduced NEFA content in serum by lowering pHSL levels.

Therapeutic efficacy of P277 against type 1 diabetes was extensively investigated and clinically evidenced. Clinical trials Phases I and II concluded promising results, while the data of P277 immunogenicity in Phase III trials represented weak responses that led to abolish medical use. But, a therapeutic performance of P277 cannot be forgotten. So, in order to exploit its therapeutic benefits and improve its immunogenicity, we developed a new analogue VP to optimize therapeutic efficacy and enhancing immunosuppressive modulations. However, new analogue was purified, and then used to immunize diabetic NOD mice to investigate antidiabetic effects through modulation of immunological status. So, DCs immune responses, relative TLRs, MyD88, and NF-Kβ1 mRNA expression on DCs and splenocytes under VP effect were tested. Circulating and intracellular cytokines were also evaluated at treated and non-treated mice. Splenic T lymphocytes proliferation (Th1 and Treg cells) were also determined. Results revealed that VP significantly down regulates DCs maturation through TLR2, TLR4, and MyD88 pathways. It also shifts DCs to a tolerogenic polarization through NF-Kβ1 pathway that mediates Th1 immunosuppression and enhances iTreg expanding in type1diabetes mice. Meanwhile, we noticed that VP significantly enhances iTreg CD25 + FoxP3+ proliferation. In conclusion, VP showed promising immune potential to modulate immune regulatory responses and shifts DCs to suppress autoreactive Th1 cells which ameliorated immunosuppressive potency in the type1 diabetic mice.

Background: Emergence agitation is a reformed state of mindfulness, which starts with a sudden form of anesthesia and progresses through the early repossession age. Thus, the purpose of this study is to evaluate 1:3 ketofol performance on children 3–15 years old undergoing adenotonsillectomy.Methods: A total of 60 children aged 3–15 years undergoing adenotonsillectomy were randomly allocated to receive low-dose ketamine 0.15 mg/kg followed by propofol 0.45 mg/kg i.v. ketofol (1:3) about 10 min before the end of surgery in comparison to 60 children aged 3–15 years who received only normal saline and dextrose. Anesthesia was induced and maintained with sevoflurane. Postoperative pain and EA were assessed with objective pain score (OPS) and the Pediatric Anesthesia Emergence Delirium (PAED) scale, respectively. EA was defined as a PAED 10 points. Recovery profile and postoperative complications were also recorded.Results: The incidence and severity of EA were found significantly lower in the ketofol group in comparison to the control group with a percentage of (13.33% vs 48.33%) (8% vs 15%) respectively (P < 0.05). Also, the time for interaction from anesthetic tainted to extubating in the ketofol set was significantly less than in the control group (P < 0.05). Interestingly, there are no opposing events such as nausea, laryngospasm, bronchospasm, hypotension, bradycardia, bleeding, or postoperative respiratory depression (respiratory rate: 0.05). Moreover, the heart rate was meaningfully higher in the control group starting at the time of tracheal extubating in comparison to the children undergone ketofol (P < 0.05). Alert score and time from painkilling tainted till liberation from PACU showed substantial significant changes at ketofol set (P < 0.05).Conclusion: Ketofol (1:3) shows significant performance to reduce postoperative agitation in the children undergone adenotonsillectomy.

Degenerative joint diseases of the hips and knees are common and are accompanied by severe pain and movement disorders. At the microscopic level, the main characteristics of osteoarthritis are the continuous destruction and degeneration of cartilage, increased cartilage extracellular matrix catabolism, decreased anabolism, increased synovial fluid, and decreased osmotic pressure. Cell volume stability is mainly regulated by ion channels, many of which are expressed in chondrocytes. These ion channels are closely related to pain regulation, volume regulation, the inflammatory response, cell proliferation, apoptosis, and cell differentiation. In this review, we focus on the important role of volume control-related ion channels in cartilage matrix remodeling and summarize current views. In addition, the potential mechanism of the volume-sensitive anion channel LRRC8A in the early occurrence of osteoarthritis is discussed. [ABSTRACT FROM AUTHOR]

Background. Osteoarthritis (OA) is one of the most common degenerative diseases worldwide. Many researchers are studying the pathogenesis of OA, however, it is still unclear. Methods. Screening and validation of OA relevant hub genes are an important part of exploring their potential molecular mechanism. Therefore, this study aims to explore and verify the mechanisms of hub genes in the OA by bioinformatics, qPCR, fluorescence and propidium iodide staining. Results. Microarray datasets GSE43923, GSE55457 and GSE12021 were collected in the Gene Expression Omnibus (GEO), including 45 samples, which divided into 23 osteoarthritis knee joint samples and 22 samples of normal knee joint. Thereafter, 265 differentiallyexpressedgenes (DEGs) were identified in all, which divided into 199 upregulated genes and 66 downregulated genes. The hub genes MAPK-14, PTPRC, PTPN12 were upregulated, while B9D1 was downregulated. In order to further confirm the expression of screening differential genes in human chondrocytes, the human chondrocytes were extracted from a joint replacement surgery and stained with toluidine blue for identification. Compared with normal chondrocytes, OA chondrocytes had high expression of COL I protein and low expression of COL II protein. The expression levels of MAPK-14, PTPRC and PTPN12 in OA chondrocytes were significantly higher than the expression levels of B9D1 in normal chondrocytes. Moreover, the inflammatory necrosis of OA chondrocytes was increased compared with the normal chondrocytes by propidium iodide staining. Conclusions. The high expression of MAPK-14 works as a promoter of chondrocytes death and an important signal of the osteoarthritis process. [ABSTRACT FROM AUTHOR]