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Introduction: The dietary inflammatory index (DII) is associated with numerous chronic noncommunicable diseases. Previous studies have shown that the pro-inflammatory DII categories are associated with abdominal and simple obesity. However, the association between DII and mortality in patients with abdominal obesity and simple overweight or obesity remains unclear. Methods: We used data from the US National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. A DII >0 (positive DII) was defined as a pro-inflammatory diet. A restricted cubic spline curve was used to describe the trend between DII and all-cause mortality. We then examined the association between DII and all-cause mortality in different body types using a Cox regression analysis and investigated the differences between sexes. Finally, the mediating effects of systemic inflammation were explored. Results: A pro-inflammatory diet increased all-cause mortality in adults with abdominal obesity (aHR: 1.31, 95% confidence interval [CI]: 1.11–1.54; p < 0.001) and with simple overweight or obesity (aHR: 1.30, 95% CI: 1.11–1.53; p < 0.001). In addition, the most pro-inflammatory DII increased the risk of mortality by 43% (hazard ratio [HR]: Q4 vs. Q1 = 1.43, 95% CI = 1.14–1.79; p = 0.002; p for trend = 0.003) and 39% (HR: Q4 vs. Q1 = 1.39, 95% CI = 1.13–1.74; p = 0.003; p for trend = 0.009) in participants with abdominal obesity and with simple overweight or obesity, respectively. However, this association was not present in normal-sized participants. Compared with men, women resisted the effects of a pro-inflammatory diet. Mediation analysis showed that white blood cell and neutrophil were mediators of the association between DII and all-cause mortality (p < 0.001). Conclusion: A pro-inflammatory diet is associated with all-cause mortality in adults with abdominal obesity and simple overweight or obesity, and this effect differs between men and women. Systemic inflammation may mediate the association between DII and all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: Aging is accompanied by muscle loss. In older adults with cancer sarcopenia (OACS), systemic inflammation, reduced food intake, and reduced physical activity led to a poor prognosis. This study was to investigate the prognostic ability of the inflammatory Geriatric Nutritional Risk Index (GNRI), which combines patient's inflammation, diet status, and physical activity status to predict overall survival of OACS. Methods: This prospective multi‐center study enrolled 637 OACS, with an average age of 72.78 ± 5.98 years, of which 408 (64.1%) were males. We constructed the Inflammatory Functional Prognostic Index (IFPI) of OACS based on inflammatory GNRI scores, reduced food intake, and reduced physical activity. According to the IFPI, OACS was divided into high‐, moderate‐, and low‐risk groups. Univariate and multivariate survival analyses analyzed the prognostic ability of the clinical parameters. Results: Compared with OACS with a high GNRI score, the 1‐, 3‐, and 5‐year hazard ratios (95% confidence interval) of OACS with a low GNRI score was 1.816 (1.076–3.063), 1.678 (1.118–2.518), and 1.627 (1.101–2.407), respectively. This result was consistent with that of the calibration curve. The subgroup analysis showed that the low GNRI score had a significant positive relation with patients with gastrointestinal cancer (Pinteraction < 0.001). Notably, the survival analysis of IFPI showed that the mortality risk of moderate‐ and high‐risk patients was 1.722‐and 2.509‐fold higher, respectively, than that of low‐risk patients. Conclusion: The GNRI score was a short‐term and long‐term inflammatory prognostic indicator for OACS. The IFPI score could improve patient survival prediction. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation and insulin resistance (IR) are closely related in patients with cancer. However, there is no relevant indicator that combines inflammation and IR to predict patient prognosis. Therefore, this study aimed to develop and validate a novel inflammation- and IR-related marker in patients with cancer. Methods: The total cohort of this study included 5221 patients with cancer, and the training and validation cohorts were randomized in a 7:3 ratio. C-reactive protein (CRP) and fasting triglyceride glucose (TyG) were used to reflect patients' inflammation and IR status, respectively. The CRP-TyG index (CTI) was composed of CRP and TyG. The concordance (C)-index, receiver operator characteristic (ROC) curve, and calibration curve reflected the prognostic predictive power of CTI. Univariate and multivariate survival analyses predicted the prognostic value of CTI in patients with cancer. Results: The C-indices of CTI in patients with cancer were 0.636, 0.617, and 0.631 in the total, training, and validation cohorts, respectively. The 1-, 3-, and 5-year ROC and calibration curves showed that CTI had a good predictive ability of survival in patients with cancer. Meanwhile, patients with high CTI had a worse prognosis compared to patients with low CTI (total cohort: hazard ratio [HR] = 1.46, 95% confidence interval [95% CI] = 1.33–1.59; training cohort: HR = 1.36, 95% CI = 1.22–1.52; validation cohort: HR = 1.73, 95% CI = 1.47–2.04]. Conclusion: The CTI is a useful prognostic indicator of poor prognosis and a promising tool for treatment strategy decision-making in patients with cancer. [ABSTRACT FROM AUTHOR]

Aging is a predominant risk factor for many chronic conditions. Stem cell dysfunction plays a pivotal role in the aging process. Prelamin A, an abnormal processed form of the nuclear lamina protein lamin A, has been reported to trigger premature senescence. However, the mechanism driving stem cell dysfunction is still unclear. In this study, we found that while passaging subchondral bone mesenchymal stem cells (SCB-MSCs) in vitro, prelamin A accumulation occurred concomitantly with an increase in senescence-associated β-galactosidase (SA-β-Gal) expression. Unlike their counterparts, SCB-MSCs with prelamin A overexpression (MSC/PLA) demonstrated decreased proliferation, osteogenesis, and adipogenesis but increased production of inflammatory factors. In a hind-limb ischemia model, MSC/PLA also exhibited compromised therapy effect. Further investigation showed that exogenous prelamin A triggered abnormal nuclear morphology, DNA and shelterin complex damage, cell cycle retardation, and eventually cell senescence. Changes in gene expression profile were also verified by microarray assay. Interestingly, we found that ascorbic acid or vitamin C (VC) treatment could inhibit prelamin A expression in MSC/PLA and partially reverse the premature aging in MSC/PLA, with reduced secretion of inflammatory factors and cell cycle arrest and resistance to apoptosis. Importantly, after VC treatment, MSC/PLA showed enhanced therapy effect in the hind-limb ischemia model. In conclusion, prelamin A can accelerate SCB-MSC premature senescence by inducing DNA damage. VC can be a potential therapeutic reagent for prelamin A-induced aging defects in MSCs. [ABSTRACT FROM AUTHOR]

Adipose-derived stem cells (ASCs) have become one of the most promising stem cell populations for cell-based therapies in regenerative medicine and for autoimmune disorders owing to their multilineage differentiation and immunomodulatory capacities, respectively. One advantage of ASC-based therapy lies in their immunosuppressive potential. However, how to get ASCs to provide consistent immunosuppression remains unclear. In the current study, we found that miR-129-5p was induced in ASCs treated with inflammatory factors. ASCs with miR-129-5p knockdown exhibited enhanced immunosuppressive capacity, as evidenced by reduced expression of proinflammatory factors, with concurrent increased expression of inducible nitric oxide synthases (iNOS) and nitric oxide (NO) production. These cells also had an increased capacity to inhibit T cell proliferation in vitro. ASCs with miR-129-5p knockdown alleviated inflammatory bowel diseases and promoted tumor growth in vivo. Consistently, ASCs that overexpressed miR-129-5p exhibited reduced iNOS expression. Furthermore, we show that miR-129-5p knockdown in ASCs results in hyperphosphorylation of signal transducer and activator of transcription 1 (Stat1). When fludarabine, an inhibitor of Stat1 activation, was added to ASCs with miR-129-5p knockdown, iNOS mRNA and protein levels were significantly reduced. Collectively, these results reveal a new role for miR-129-5p in regulating the immunomodulatory activities of ASCs by targeting Stat1 activation. These novel insights into the mechanisms of ASC immunoregulation may lead to the consistent production of ASCs with strong immunosuppressive functions and thus better clinical utility of these cells. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC., Methods: The clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage., Results: Multivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P <0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P <0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P <0.001) than the TNM stage., Conclusion: The CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage., 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 © 2023 Yang, Lin, Liu, Tang, Hu, Wang, Zhang, Zhang, Song, Ruan, Zhang, Liu, Xie, Zhang, Liu, Zhang, Li, Li, Ge, Liu, Chen, Zheng and Shi.)

Purpose: Previous studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility., Methods: This was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan-Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used., Results: A total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidence interval [CI],1.14-1.98; p  = 0.001 and HR, 1.55; 95% CI, 1.14-2.12, p  = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52-3.63; p  < 0.001). The area under the curve of HGS-mGPS was 0.623. The calibration curve demonstrated the validity of the HGS-mGPS nomogram model for predicting the survival of patients with liver cancer., Conclusion: A combination of low HGS and high mGPS is associated with poor prognosis in patients with liver cancer. The combination of HGS and mGPS can predict the prognosis of liver cancer more accurately than HGS or mGPS alone. The nomogram model developed in this study can effectively predict the survival outcomes of liver cancer., 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 © 2023 Chen, Ruan, Shi, Liu, Liu, Xie, Song, Wang, Hu, Zhang, Zhang, Tian, Ge, Yang, Liu, Lin, Liu, Zheng, Wang, Cong, Shen, Wang, Deng and Shi.)

Background: Central obesity is closely related to comorbidity, while the relationship between fat accumulation pattern and abnormal distribution in different parts of the central region of obese people and comorbidity is not clear. This study aimed to explore the relationship between fat distribution in central region and comorbidity among obese participants., Methods: We used observational data of NHANES 2011-2018 to identify 12 obesity-related comorbidities in 7 categories based on questionnaire responses from participants. Fat distribution is expressed by fat ratio, including Android, Gynoid, visceral, subcutaneous, visceral/subcutaneous (V/S), and total abdominal fat ratio. Logistic regression analysis were utilized to elucidate the association between fat distribution and comorbidity., Results: The comorbidity rate was about 54.1% among 4899 obese participants (weighted 60,180,984, 41.35 ± 11.16 years, 57.5% female). There were differences in fat distribution across the sexes and ages. Among men, Android fat ratio (OR, 4.21, 95% CI, 1.54-11.50, P trend =0.007), visceral fat ratio (OR, 2.16, 95% CI, 1.42-3.29, P trend <0.001) and V/S (OR, 2.07, 95% CI, 1.43-2.99, P trend <0.001) were independent risk factors for comorbidity. Among these, there was a "J" shape correlation between Android fat ratio and comorbidity risk, while visceral fat ratio and V/S exhibited linear relationships with comorbidity risk. The Gynoid fat ratio (OR, 0.87, 95%CI, 0.80-0.95, P trend =0.001) and subcutaneous fat ratio (OR, 0.81, 95%CI, 0.67-0.98, P trend =0.016) both performed a protective role in the risk of comorbidity. In women, Android fat ratio (OR, 4.65, 95% CI, 2.11-10.24, P trend =0.020), visceral fat ratio (OR, 1.83, 95% CI, 1.31-2.56, P trend =0.001), and V/S (OR, 1.80, 95% CI, 1.32-2.45, P trend =0.020) were also independent risk factors for comorbidity, with a dose-response relationship similar to that of men. Only the Gynoid fat ratio (OR, 0.93, 95% CI, 0.87-0.99, P trend =0.016) had a protective effect on female comorbidity. This association was also seen in obese participants of different age groups, comorbidity numbers, and comorbidity types, although it was more statistically significant in older, complex comorbidity, cardiovascular, cerebrovascular, and metabolic diseases., Conclusions: In the obese population, there were strong correlation between fat distribution in central region and comorbidity, which was affected by sex, age, number of comorbidities, and type of comorbidity., 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 © 2023 Liu, Liu, Ruan, Ge, Song, Xie, Lin, Deng, Zhang, Zhang and Shi.)

Background: Systemic inflammation and water composition are important factors affecting cancer prognosis. This study aimed to explore the association between the neutrophil-to-lymphocyte ratio (NLR) and intracellular water/total body water (ICW/TBW) ratio and overall survival (OS) in colorectal cancer (CRC)., Methods: This multicenter, prospective cohort included 628 patients with CRC between June 2012 and December 2019. The association between the covariates and OS was assessed using a Cox proportional hazards model and restricted cubic spline models. Concordance index (C-index), which integrated discriminant improvement (IDI) index and continuous net reclassification index, (cNRI) was used to compare the predictive ability of the markers., Results: The optimal cutoff values for the NLR and ICW/TBW ratio were 2.42 and 0.61, respectively. The NLR was negatively associated with OS, while the ICW/TBW ratio was positively correlated with OS. NLR ≥2.42 and ICW/TBW ratio <0.61 were both independent poor prognostic factors (hazard ratio [HR]: 2.04, 95% confidence interval [CI]: 1.44-2.88 and HR: 1.45, 95% CI: 1.04-2.02, respectively). Subsequently, we combined the two factors to construct an inflammation-water score (IWS). Patients with IWS (2, ≥1) had worse OS (HR: 2.86 and 95% CI: 1.77-4.63; HR: 1.74 and 95% CI 1.17-2.57, respectively) than those without one. Compared to its component factors, IWS score showed better predictive ability for C-index, IDI index, and cNRI., Conclusion: A high NLR and a low ICW/TBW ratio were independent risk factors for poor prognosis in patients with CRC. The combination of the two factors can provide a better prognostic prediction effect., 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 © 2022 Lin, Xie, Ge, Ruan, Zhang, Song, Zhang, Zhang, Li, Tang, Shen, Song, Li and Shi.)

Background: Elderly patients with cancer face the challenge of systemic inflammation, which can lead to a poor prognosis. Existing inflammatory indices cannot fully reflect the immune-inflammatory status of patients. This study aimed to develop a new scoring system to predict the survival of elderly patients with cancer using inflammatory indices, namely, the systemic inflammation prognostic score (SIPS)., Materials and Methods: This prospective multicenter study included a total of 1,767 patients with cancer, with a mean age of 70.97 ± 5.49 years, of whom 1,170 (66.2%) were men. We performed the least absolute shrinkage and selection operator (LASSO) regression to screen inflammatory indicators to include in constructing SIPS. Prognostic analysis of SIPS was performed using univariate and multivariate survival analyzes. The prognostic value of SIPS and its components were compared using the prognostic receiver operating characteristic curve and concordance index. The population was divided into the training cohort and the validation cohort in a 7:3 ratio and a SIPS prognostic analysis was performed., Results: The LASSO regression selected C-reactive protein (CRP) (≤ 9.81, "0"; > 9.81, "1"), geriatric nutritional risk index (GNRI) (≤ 93.85, "1"; 93.85, "0"), advanced lung cancer inflammation index (ALI) (≤ 23.49, "1"; > 23.49, "0"), and lymphocyte to C-reactive protein ratio (LCR) (≤ 2523.81, "1"; > 2523.81, "0") to develop SIPS. Patients were divided into the three groups based on the total SIPS: low-risk (0), moderate-risk (1-2), and high-risk (3-4). On the multivariate survival analysis, patients in the moderate-risk [ P < 0.001, hazard ratio (HR) = 1.79, 95% CI: 1.47-2.17] and high-risk groups ( P < 0.001, HR = 2.40, 95% CI: 1.98-2.92) showed a worse prognosis than those in the low-risk group. The total cohort, training cohort, and validation cohort all showed that SIPS had better survival prediction than CRP, GNRI, ALI, and LCR. The HRs were 2.81 times higher in patients in the high-risk group with malnutrition than in patients in the low-risk group without malnutrition., Conclusion: SIPS was an independent prognostic indicator in elderly patients with cancer. Malnutrition in the high-risk group increased the mortality risk., 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. The reviewer JG declared a shared affiliation with one of the author Y-ZGo to the handling editor at the time of review., (Copyright © 2022 Ruan, Xie, Deng, Ge, Zhang, Wang, Zhang, Zhang, Tang, Song, Zhang, Yang, Pan, Wang, Cong, Gong, Wang and Shi.)

Background: Non-small cell lung cancer (NSCLC) is among the most prevalent malignancies worldwide. Previous studies have shown that the status of inflammation, nutrition and immune are closely related to overall survival (OS) of patients with NSCLC, but little is known about their interactive and combined roles. Hence, we chose glucose to lymphocyte ratio (GLR) and modified Glasgow Prognosis Score (mGPS) as prognostic factors and assessed the prognostic values of them for patients with NSCLC., Methods: Baseline clinicopathologic and laboratory characteristics of 862 patients with NSCLC were obtained from a multicenter prospective cohort. The Cox proportional hazard regression models were used to determine prognostic values of the clinical factors. A nomogram was also constructed integrating the clinical factors with clinical significance or independent prognostic values. Concordance index (C-index) was utilized to evaluate the prediction accuracy of the TNM stage and the nomogram., Results: Multivariate analyses demonstrated that GLR [Hazard ratio (HR) = 1.029, 95% confidence interval (CI) = 1.004-1.056, P = 0.023] and mGPS (score of 1: HR = 1.404, 95% CI = 1.143-1.726, P = 0.001; score of 2: HR = 1.515, 95% CI = 1.159-1.980, P = 0.002) were independent prognostic factors for patients with NSCLC. The C-indexes of the TNM stage and the nomogram were 0.642 (95% CI = 0.620-0.663) and 0.694 (95% CI = 0.671-0.717), respectively., Conclusion: GLR and mGPS were independent prognostic factors for patients with NSCLC. Moreover, our constructed nomogram might be superior in predicting prognosis of patients with NSCLC compared with the TNM stage., 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 © 2022 Yang, Zhang, Ge, Tang, Hu, Wang, Zhang, Song, Ruan, Zhang, Liu, Xie, Zhang, Zhang, Li, Li, Liu, Lin and Shi.)

Background and Objectives: The effective use of MSCs for the treatment of some B cell-mediated immune diseases is quite limited. The main reason is that the immunomodulatory effects of mesenchymal stem cells (MSCs) on B cells are unclear, and their underlying mechanisms have not been fully explored., Methods and Results: By co-culturing B cells with MSCs without (MSC/CTLsh) or with suppressor of cytokine signaling 1 (SOCS1) knockdown (MSC/SOCS1sh), we found that MSCs inhibited B cell proliferation, activation and terminal differentiation. Remarkably, the highest inhibition of B cell proliferation was observed in MSC/SOCS1sh co-culture. Besides, MSC/SOCS1sh reversed the inhibitory effect of MSCs in the last stage of B cell differentiation. However, MSC/SOCS1sh had no effect on inhibiting B cell activation by MSCs. We also showed that IgA + B cell production was significantly higher in MSC/SOCS1sh than in MSC/CTLsh, although no difference was observed when both MSCs co-cultures were compared to isolated B cells. In addition, MSCs increased PGE2 production after TNF- α /IFN- γ stimulation, with the highest increase observed in MSC/SOCS1sh co-culture., Conclusions: Our results highlighted the role of SOCS1 as an important new mediator in the regulation of B cell function by MSCs. Therefore, these data may help to develop new treatments for B cell-mediated immune diseases.