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Context: Over 1.9 billion adult people have overweight or obesity. Considered as a chronic disease itself, obesity is associated with several comorbidities. Chronic pain affects approximately 60 million people and its connection with obesity has been displayed in several studies. However, controversial results showing both lower and higher pain thresholds in subjects with obesity compared to individuals with normal weight and the different parameters used to define such association (e.g., pain severity, frequency or duration) make it hard to draw straight forward conclusions in the matter. The objective of this article is to examine the relationship between overweight and obesity (classified with BMI as recommended by WHO) and self-perceived pain intensity in adults., Methods: A literature search was conducted following PRISMA guidelines using the databases CINAHL, Cochrane Library, EMBASE, PEDro, PubMed, Scopus and Web of Science to identify original studies that provide BMI values and their associated pain intensity assessed by self-report scales. Self-report pain scores were normalized and pooled within meta-analyses. The Cochrane's Q test and I 2 index were used to clarify the amount of heterogeneity; meta-regression was performed to explore the relationship between each outcome and the risk of bias., Results: Of 2194 studies, 31 eligible studies were identified and appraised, 22 of which provided data for a quantitative analysis. The results herein suggested that adults with excess weight (BMI ≥ 25.0) or obesity (BMI ≥ 30.0) but not with overweight (pre-obesity) alone (BMI 25.0-29.9), are more likely to report greater intensities of pain than individuals of normal weight (BMI 18.5-24.9). Subgroup analyses regarding the pathology of the patients showed no statistically significant differences between groups. Also, influence of age in the effect size, evaluated by meta-regression, was only observed in one of the four analyses. Furthermore, the robustness of the findings was supported by two different sensitivity analyses., Conclusion: Subjects with obesity and excess weight, but not overweight, reported greater pain intensities than individuals with normal weight. This finding encourages treatment of obesity as a component of pain management. More research is required to better understand the mechanisms of these differences and the clinical utility of the findings., Systematic Review Registration: https://doi.org/10.17605/OSF.IO/RF2G3, identifier OSF.IO/RF2G3., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Garcia, Corrales, Huerta, Czachorowski, López-Miranda, Medina-Gómez, Cobos, Goicoechea and Molina-Álvarez.)

Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital-based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis., (© 2017 UICC.)

Background: Inadequate or excessive nociceptive control during general anesthesia can result in significant adverse outcomes. Using traditional clinical variables, such as heart rate, systolic blood pressure, and respiratory rate, to assess and manage nociceptive responses is often insufficient and could lead to overtreatment with both anesthetics and opioids. This study evaluated the feasibility and effectiveness of three nociception monitoring techniques Nociception Level Index (NOL), Skin Conductance Algesimeter (SCA) and heart rate monitoring in patients undergoing image-guided, minimally invasive abdominal interventions under general anesthesia. Method: This prospective observational study collected data from 2022 to 2024. All patients were anesthetized according to the department's routine, and predetermined events were recorded. Two commercially available nociception monitors, the PMD-200 from Medasense (NOL) and PainSensor from MedStorm (SCA), were used, and their data were collected along with various hemodynamic parameters. The three nociception monitoring techniques were compared during predetermined events. Result: A total of 49 patients were included in this study. NOL and SCA demonstrated higher responsiveness than HR for all events except for skin incision. The comparison of the values above and below the threshold for each nociceptive stimulus showed significance for all measurements using the SCA and NOL. However, using HR as a surrogate for nociception with a threshold of a 10% increase from baseline, the difference was significant only at skin incision. There was no variation in the peak values attributable to differences in patients' age. Weight was a significant predictor of the peak NOL values. Conclusion: NOL and SCA demonstrated superior sensitivity and responsiveness to nociceptive stimuli compared to HR, effectively detecting significant changes in nociceptive thresholds across various stimuli, although responses during skin incision showed no such advantage. Trial registration: Clinical trial - NCT05218551. [ABSTRACT FROM AUTHOR]

Aberrant overexpression of cyclooxygenase-2 (COX2) is observed in urothelial carcinoma of the bladder (UCB). Studies evaluating COX2 as a prognostic marker in UCB report contradictory results. We determined the prognostic potential of COX2 expression in UCB and quantitatively summarize the results with those of the literature through a meta-analysis. Newly diagnosed UCB patients recruited between 1998-2001 in 18 Spanish hospitals were prospectively included in the study and followed-up (median, 70.7 months). Diagnostic slides were reviewed and uniformly classified by expert pathologists. Clinical data was retrieved from hospital charts. Tissue microarrays containing non-muscle invasive (n=557) and muscle invasive (n=216) tumours were analyzed by immunohistochemistry using quantitative image analysis. Expression was evaluated in Cox regression models to assess the risk of recurrence, progression and disease-specific mortality. Meta-hazard ratios were estimated using our results and those from 11 additional evaluable studies. COX2 expression was observed in 38% (211/557) of non-muscle invasive and 63% (137/216) of muscle invasive tumors. Expression was associated with advanced pathological stage and grade (p<0.0001). In the univariable analyses, COX2 expression - as a categorical variable - was not associated with any of the outcomes analyzed. As a continuous variable, a weak association with recurrence in non-muscle invasive tumors was observed (p-value=0.048). In the multivariable analyses, COX2 expression did not independently predict any of the considered outcomes. The meta-analysis confirmed these results. We did not find evidence that COX2 expression is an independent prognostic marker of recurrence, progression or survival in patients with UCB.

The purpose of this study was to systematically examine the association between bronchial asthma and lung cancer. Research on the correlation between bronchial asthma and lung cancer was retrieved from the database. Literature was screened based on inclusion and exclusion criteria, and the number of patients in the included studies was extracted and analyzed. This study used Stata statistical software version 16.0 and Cochrane Review Manager version 5.4 for meta-analysis. In our study, 19 articles were selected. Without considering other influencing factors, the risk of lung cancer in asthma patients was relative risk (RR)=1.40 (95% CI: 1.17-1.67, I2=55.7%), and after correcting for risk factors such as smoking and age, it was found that the risk of small-cell lung cancer in asthma patients was RR=2.11 (95% CI: 1.45-3.24). Asthma may increase the risk of developing lung cancer, with an even higher likelihood for small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a significant global health issue, suspected to elevate the risk for various cancers. This study sought to discern whether COPD serves as a risk marker or a causative factor for prevalent cancers. Methods: We employed univariable MR (UVMR) analyses to investigate the causal relationship between COPD and the top ten common cancers. Sensitivity analyses were performed to validate the main findings. Multivariable MR (MVMR) and two-step MR analyses were also conducted. False-discovery-rate (FDR) was used to correct multiple testing bias. Results: The UVMR analysis demonstrated notable associations between COPD and lung cancer (odds ratio [OR] = 1.42, 95%CI 1.15–1.77, FDR = 6.37 × 10–3). This relationship extends to lung cancer subtypes such as squamous cell carcinoma (LUSC), adenocarcinoma (LUAD), and small cell lung cancer (SCLC). A tentative link was also identified between COPD and bladder cancer (OR = 1.53, 95%CI 1.03–2.28, FDR = 0.125). No significant associations were found between COPD and other types of cancer. The MVMR analysis that adjusted for smoking, alcohol drinking, and body mass index did not identify any significant causal relationships between COPD and either lung or bladder cancer. However, the two-step MR analysis indicates that COPD mediated 19.2% (95% CI 12.7–26.1%), 36.1% (24.9–33.2%), 35.9% (25.7–34.9%), and 35.5% (26.2–34.8%) of the association between smoking and overall lung cancer, as well as LUAD, LUSC, and SCLC, respectively. Conclusions: COPD appears to act more as a risk marker than a direct cause of prevalent cancers. Importantly, it partially mediates the connection between smoking and lung cancer, underscoring its role in lung cancer prevention strategies. [ABSTRACT FROM AUTHOR]

Microbial-induced inflammation serves a dual role, safeguarding against pathogens but also posing a risk of secondary harm to host tissues, potentially leading to fibrosis and cancer. Beyond traditional pathogens, gut microbiota, the mutualistic microorganisms inhabiting the gastrointestinal tract, crucial for digestion, immunity, and cancer prevention, can incite inflammation-related cancer when their microenvironment undergoes changes. Recent research reveals that microbiota members like Escherichia coli and other genotoxic pathogens can induce DNA damage across various cell types. Chronic infections involving microbiota members like Helicobacter spp., linked to liver, colorectal, cervical cancers, and lymphoma, can activate carcinogenic processes. Inflammatory responses, driven by immune cells releasing inflammatory molecules like macrophage migration inhibitory factor (MMIF), superoxide peroxynitrite, pro-inflammatory cytokines, adhesion molecules, and growth factors, contribute to DNA damage and oncogenic mutations accumulation. This microenvironment further supports neoplastic cell survival and proliferation. This summary discusses the involvement of inflammatory pathways in microbial-triggered carcinogenesis and the potential role of microbiota modulation in cancer prevention. [ABSTRACT FROM AUTHOR]

While activation of immune system may lead to a lower risk of some diseases, it has been shown that a history of atopic allergic disorders such as asthma, hay fever, eczema, and food allergies could be related to several types of cancer. However, the evidence is not entirely conclusive. Two proposals suggest a possible mechanism for the association between allergic disorders and cancers: immune surveillance and the antigenic stimulation. The association of allergy and cancer may vary by cancer site and the type of exposure. The aim of current review was to summarize the current knowledge of the association between allergic diseases and the risk of cancers with particular emphasis on case-controls and cohort studies to estimate the cancer risk associated with allergy., (© 2020 International Union of Biochemistry and Molecular Biology.)

Xuebijing injection (XBJ), one of the classical prescriptions for treating inflammation-related diseases, has been used to chronic obstructive pulmonary disease (COPD) in clinical practice. However, its molecular mechanism is still unclear. Network pharmacology combined with Affymetrix arrays and molecular docking techniques were applied to explore the molecular mechanism of XBJ for COPD. Predictive analysis of 728 active compounds in XBJ and 6 sets of Affymetrix arrays expression data resulted in 106 potential therapeutic targets. Next, based on the active compound-co-target network topology analysis, most of these targets were found to be modulated by quercetin, myricetin, and ellagic acid. Furthermore, protein–protein interaction (PPI) analysis revealed that the key targets may be EGFR, STAT3, AKT1, CCND1, MMP9, AR, ESR1, and PTGS2. Then, by constructing a component-target-pathway network, we found that XBJ was a multi-pathway, multi-target, multi-compound synergistic therapy for COPD, and four key targets were involved in the FoxO signaling pathway. Luteolin and salvianolic acid b had the optimal binding ability to several key proteins. Therefore, we hypothesize that quercetin, myricetin, ellagic acid, luteolin, and salvianolic acid b mainly contribute to the therapeutic effect of XBJ on COPD by modulating the FoxO signaling pathway by regulating EGFR, STAT3, AKT1, and CCND1. XBJ exerts anti-inflammatory and antioxidative stress effects through the PI3K/Akt/FoxO axis combined with MMP9, AR, ESR1, and PTGS2 to regulate other signaling pathways. [ABSTRACT FROM AUTHOR]

Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (P =0.175). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in female patients (P =0.063). However, the male population who regularly took aspirin had a lower incidence of BCa (OR=0.748, 95% CI= 0.584-0.958, P =0.021). Subgroup analyses stratified by smoking found a significant reduction in the risk of BCa in current smokers with aspirin intake (OR=0.522, 95% CI=0.342-0.797, P =0.002). In terms of prognosis of BCa, patients with a history of aspirin intake did not had a markedly longer OS or RFS than those with no history of aspirin intake by Kaplan-Meier curves. Stratified analysis by sex showed no correlation between aspirin intake and the recurrence or survival of BCa for either male or female patients. However, in people younger than 68, aspirin intake seemed to have prolonged effects for overall survival (HR=3.876; 95% CI=1.326-11.325, P =0.019). Then, we performed a meta-analysis and the combined results from 19 articles and our study involving more than 39524 BCa cases indicated that aspirin intake was not associated with the occurrence of BCa (P =0.671). Subgroup analysis by whether regular use of aspirin, by the mean duration of use of aspirin, by sex, by smoking exposure, by research region and by study type also supported the above results. In terms of the impact of aspirin intake on the prognosis of patients with BCa, 11 articles and our study involving 8825 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have significantly influence on survival, recurrence, progression and metastasis than those without aspirin intake. On the whole, both our retrospective study and literature meta-analysis suggested a lack of a strong relevant association between the use of aspirin and the incidence or prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis. [ABSTRACT FROM AUTHOR]

Recent epidemiological studies have indicated that occupational exposure to the aromatic amine acetoaceto-o-toluidide (AAOT) was associated with a marked increase in urinary bladder cancers in Japan. However, little is known about the carcinogenicity of AAOT. To evaluate the urinary bladder carcinogenicity of AAOT, male and female F344 rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks followed by dietary administration of 0, 0.167, 0.5, or 1.5% AAOT for 31 weeks. The incidences and multiplicities of bladder tumors were significantly increased in the 0.5 and 1.5% groups of male and female rats in a dose-response manner. AAOT and seven downstream metabolites were detected in the urine of the male and female rats administered AAOT with levels increasing in a dose-dependent manner. The most abundant urinary metabolite of AAOT was the human bladder carcinogen o-toluidine (OTD), which was at least one order of magnitude higher than AAOT and the other AAOT metabolites. In a second experiment, male F344 rats were administered 0, 0.167, or 1.5% AAOT for 4 weeks. Gene expression analyses revealed that the expression of JUN and its downstream target genes was increased in the urothelium of male rats treated with 1.5% AAOT. These results demonstrate that AAOT promotes BBN-induced urinary bladder carcinogenesis in rats and suggest that overexpressed of JUN and its downstream target genes may be involved the bladder carcinogenicity of AAOT. In conclusion, AAOT, like other carcinogenic aromatic amines, is likely to be a carcinogen to the urinary bladder, and OTD metabolized from AAOT is the ultimate carcinogen. [ABSTRACT FROM AUTHOR]

The inducible inflammatory enzyme cyclooxygenase‐2 (COX‐2) and its product prostaglandin E2 (PGE2) are prominent tumour promoters, and expression of COX‐2 is elevated in a number of tumours of both humans and canines. Targeting COX‐2 in cancer is an attractive option because of readily available non‐steroidal anti‐inflammatory drugs (NSAIDs), and there is a clear epidemiological link between NSAID use and cancer risk. In this study, we aim to establish the anti‐tumourigenic effects of the selective, long‐acting COX‐2 inhibitor mavacoxib. We show here that mavacoxib is cytotoxic to a panel of human and canine osteosarcoma, mammary and bladder carcinoma cancer cell lines; that it can induce apoptosis and inhibit the migration of these cells. Interestingly, we establish that mavacoxib can exert these effects independently of elevated COX‐2 expression. This study highlights the potential novel use of mavacoxib as a cancer therapeutic, suggesting that mavacoxib may be an effective anti‐cancer agent independent of tumour COX‐2 expression. [ABSTRACT FROM AUTHOR]

Introduction: Overexpression of cyclooxygenase-2 (COX2) in urothelial carcinoma of bladder (UCB) had been studied in the past by different workers and the results were contradictory. The objective of the present study was to evaluate the prognostic implication of COX2 expression in primary urothelial carcinomas of the urinary bladder and its correlation with clinical parameters, tumor stage, grade, and recurrence. Materials and methods: A total of 68 cases who underwent surgery for urothelial carcinoma in our medical college from January 2013 to December 2015 were evaluated in our study. Hematoxylin and eosin-stained slides were examined by two faculties applying standard reporting protocol. Tumor staging and grading was performed as per the WHO guidelines. Immunohistochemistry for expression of COX2 was performed to study any correlation of tumor grade with COX2 expression. The distribution of COX2 positivity was studied in tumors stratified according to established bladder cancer prognostic factor, for example, tumor size, grade, invasion, and spread. Results: Out of 68 cases, 42 cases showed COX2 positivity (61%). In low-grade cases of bladder carcinoma, COX2 positivity was 16 out of 24 cases (60%), and in high-grade cases, COX2 positivity was 10 out of 18 cases (64.28%). Conclusion: In the present study, the association of COX2 overexpression with advanced tumor invasion and tumor grade has been substantiated. Hence, COX2 expression can be taken as a prognostic factor along with other usual prognostic factors in patients of UCB. [ABSTRACT FROM AUTHOR]

This paper provides detailed insight into the mechanisms of repair of different types of DNA damage and the direct molecular players (enzymes repairing the damage or tagging the damaged site for further processing; damage sensor molecules; other signalling and effector molecules). The genetic bases of diseases and condions associated with defective DNA repair are comprehensively reviewed, from the 'classic' severe diseases such as xeroderma pigmentosum and Cockayne syndrome to the much more subtle UV sensitivity syndromes. The review analyses the basic molecular mechanisms underlying the relatively rare monogenic diseases of DNA repair and management of genome integrity as well as the common multifactorial diseases and conditions with late onset that are associated with increased levels of oxidative stress (metabolic syndrome, diabetes type 2, cardiovascular disease) and with accumulation of 'errors' in DNA (normal and pathological ageing phenotypes, various cancers). The role of cell cycle checkpoints in dividing cells and the mechanisms of decision-making for the fate of a damaged cell are discussed with regards to the cell homeostasis in normal and cancerous issues. The role of major DNA damage-associated signalling and effector molecules (p53, ATM, poly-(ADP-ribose)-polymerase, DNA-dependent protein kinase, BRCA proteins, retinoblastoma protein, and others) is discussed and illustrated with examples in the context of health and disease. DNA repair and programmed cell death are viewed together as a unified mechanism for limiting the presence of damaged cells and cells with potentially oncogenic transformation in multicellular organisms. Special attention is paid to ageing as a natural phenomenon and an adaptive evolutionary mechanism, with a brief outline of 'successful ageing'. The differential rates of repair of DNA in transcribed and nontranscribed regions of the genome and the specificities of DNA repair profile in some types of cells (terminally differentiated cells, pluripotent stem cells, etc.) and in certain taxonomic groups (e.g. 'the rodent repairadox') are discussed with regards to replicative ageing and the evolutionary processes on micro- and macroscale. The role of mutagenesis as a 'hit and miss' mechanism and the 'leakiness' of DNA repair for increasing genetic diversity in the course of individual life and on evolutionary scale and the phenomenology of ongoing molecular evolution are extensively reviewed. [ABSTRACT FROM AUTHOR]

Background: Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. The Ki-67 antigen is a classic marker of cellular proliferation, but there is still controversy regarding the significance and importance of Ki-67 in tumor progression. Methods: In this study, we first detected Ki-67 expression in UTUC patients by immunohistochemistry (IHC). Subsequently, we quantitatively combined the results with those from the published literature in a meta-analysis after searching several databases. Results: IHC results demonstrated that patients with muscle-invasive tumors (T2-T4) had higher Ki-67 expression than those with non-muscle-invasive tumors (Tis-T1), suggesting that high Ki-67 expression may be associated with the aggressive form of UTUC. Kaplan-Meier curves showed that patients with high Ki-67 expression had significantly poorer cancer-specific survival (CSS) and disease-free survival (DFS). Furthermore, multivariate analysis suggested that Ki-67 expression was an independent prognostic factor for CSS (hazard ratio, HR=3.196) and DFS (HR=3.517) in UTUC patients. Then, a meta-analysis of the published literature investigating Ki-67 expression and its effects on UTUC prognosis was conducted. After searching the PubMed, Medline, Embase, Cochrane Library and Scopus databases, 12 articles met the eligibility criteria for this analysis. The eligible studies included a total of 1740 patients with a mean number of 82 patients per study (range, 38-475). The combined results showed that increased Ki-67 levels were associated with poor survival and disease progression, with a pooled HR estimate of 2.081 and 2.791, respectively. In subgroup analysis, the pooled HR was statistically significant for cancer-specific survival (HR=2.276), metastasis-free survival (HR=3.008) and disease-free survival (HR=6.336). Conclusions: In conclusion, high Ki-67 expression was associated with poor survival in patients with UTUC, as well as a high risk of disease progression, although these findings need to be interpreted with caution. Large-scale, adequately designed, prospective trials are needed to further confirm the value of Ki-67 in prognosis of UTUC patients. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the most aggressive urothelial tumors. Previous studies have suggested that epithelial-mesenchymal transition (EMT) contributes to bladder cancer progression. However, the regulatory network of EMT in bladder cancer remains elusive. In this study, we found Yin Yang 1 (YY1) is a critical regulator of EMT in bladder cancer. First, we showed that YY1 was upregulated in bladder cancer tissues than that in adjacent normal tissues. Then, we proved that YY1 promoted EMT of bladder cancer cells. Further experiments indicated that YY1 affected the EMT of bladder cancer through transforming growth factor-β (TGFβ) signaling pathway. Taken together, our study identifies YY1 as a key EMT driver in bladder cancer, suggesting it as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Activated choline metabolism is a hallmark of carcinogenesis and tumor progression, which leads to elevated levels of phosphocholine and glycerophosphocholine in all types of cancer tested so far. Magnetic resonance spectroscopy applications have played a key role in detecting these elevated choline phospholipid metabolites. To date, the majority of cancer‐related studies have focused on phosphocholine and the Kennedy pathway, which constitutes the biosynthesis pathway for membrane phosphatidylcholine. Fewer and more recent studies have reported on the importance of glycerophosphocholine in cancer. In this review article, we summarize the recent literature on glycerophosphocholine metabolism with respect to its cancer biology and its detection by magnetic resonance spectroscopy applications. [ABSTRACT FROM AUTHOR]