The oxidized form of nicotinamide adenine dinucleotide (NAD+) is a critical metabolite for living cells. NAD+ may act either as a cofactor for many cellular reactions as well as a coenzyme for ...different NAD+-consuming enzymes involved in the physiological homeostasis of different organs and systems. In mammals, NAD+ is synthesized from either tryptophan or other vitamin B3 intermediates that act as NAD+ precursors. Recent research suggests that NAD+ precursors play a crucial role in maintaining the integrity of the gut barrier. Indeed, its deficiency has been associated with enhanced gut inflammation and leakage, and dysbiosis. Conversely, NAD+-increasing therapies may confer protection against intestinal inflammation in experimental conditions and human patients, with accumulating evidence indicating that such favorable effects could be, at least in part, mediated by concomitant changes in the composition of intestinal microbiota. However, the mechanisms by which NAD+-based treatments affect the microbiota are still poorly understood. In this context, we have focused specifically on the impact of NAD+ deficiency on intestinal inflammation and dysbiosis in animal and human models. We have further explored the relationship between NAD+ and improved host intestinal metabolism and immunity and the composition of microbiota in vivo. Overall, this comprehensive review aims to provide a new perspective on the effect of NAD+-increasing strategies on host intestinal physiology.
The purpose of this study was to explore the influence of quality of opposition and match location on game-related statistics in the Chinese Football Super League (CSL). Seven hundred and twenty ...matches from season 2014 to 2016 of CSL were analysed and all teams were classified into two groups according to their final rankings at the end of each season. The game-related statistics were divided into goal scored, offensive, defensive, and physical variables. Mann-Whitney U-test with effect size at 95% of confidence interval, and Discriminant analyses were used. Results showed a home advantage (HA) near 60%. In addition, home teams showed significantly higher average values in performance indicators regardless of the team's quality, especially in goal (score: 1.55 vs. 1.22; ES = 0.27 ± 0.10, and shots: 13.29 vs. 11.01; ES = 0.47 ± 0.10) and offence variables (possession: 0.51 vs. 0.49; ES = 0.33 ± 0.10). According to quality of opposition, superior teams played better at home in attacking categories like goal scored (1.83 vs. 1.39; ES = 0.34 ± 0.15) and offensive (possession: 0.53 vs. 0.51; ES = 0.33 ± 0.14). In conclusion, superior and inferior teams experience HA differently. These findings can help coaches to manage their team's performance according to the contextual variables that influence on performance, especially about match location and quality of opposition.
Abbreviations: Home advantage (HA); Chinese Football Super League (CSL)
The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its ...predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), where virion budding takes place. Several reports claim that E protein promotes the formation of "cation-selective channels". However, whether this term represents specificity to certain ions (e.g., potassium or calcium) or the partial or total exclusion of anions is debatable. Herein, we discuss this claim based on the available data for SARS-CoV-1 and -2 E and on new experiments performed using the untagged full-length E protein from SARS-CoV-2 in planar lipid membranes of different types, including those that closely mimic the ERGIC membrane composition. We provide evidence that the selectivity of the E-induced channels is very mild and depends strongly on lipid environment. Thus, despite past and recent claims, we found no indication that the E protein forms cation-selective channels that prevent anion transport, and even less that E protein forms
specific calcium channels. In fact, the E channel maintains its multi-ionic non-specific neutral character even in concentrated solutions of Ca
ions. Also, in contrast to previous studies, we found no evidence that SARS-CoV-2 E channel activation requires a particular voltage, high calcium concentrations or low pH, in agreement with available data from SARS-CoV-1 E. In addition, sedimentation velocity experiments suggest that the E channel population is mostly pentameric, but very dynamic and probably heterogeneous, consistent with the broad distribution of conductance values typically found in electrophysiological experiments. The latter has been explained by the presence of proteolipidic channel structures.
Macrophages have emerged as important therapeutic targets in many human diseases. The aim of this study was to analyze the effect of broccoli membrane vesicles and sulphoraphane (SFN), either free or ...encapsulated, on the activity of human monocyte-derived M1 and M2 macrophage primary culture. Our results show that exposure for 24 h to SFN 25 µM, free and encapsulated, induced a potent reduction on the activity of human M1 and M2 macrophages, downregulating proinflammatory and anti-inflammatory cytokines and phagocytic capability on C. albicans. The broccoli membrane vesicles do not represent inert nanocarriers, as they have low amounts of bioactive compounds, being able to modulate the cytokine production, depending on the inflammatory state of the cells. They could induce opposite effects to that of higher doses of SFN, reflecting its hormetic effect. These data reinforce the potential use of broccoli compounds as therapeutic agents not only for inflammatory diseases, but they also open new clinical possibilities for applications in other diseases related to immunodeficiency, autoimmunity, or in cancer therapy. Considering the variability of their biological effects in different scenarios, a proper therapeutic strategy with Brassica bioactive compounds should be designed for each pathology.
Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker ...for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients’ clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.
Abstract Context Uncertainty remains about the extent and indications for inguinal lymphadenectomy in penile cancer, a procedure known for relatively high morbidity. Several attempts have been made ...to develop strategies which can improve the diagnostic quality and reduce the morbidity of the management of inguinal lymph nodes in penile cancer. Objective To analyse the existing published data on the surgical management of inguinal nodes in penile cancer regarding morbidity and survival. Evidence acquisition A Medline search was performed of the English-language literature (1966–September 2008) using the MeSH terms penile carcinoma , lymph node dissection , lymphadenectomy , and complications. Evidence synthesis Lymph node metastases are frequent in penile cancer, even in early pT1G2 stages. Since the results of systemic treatment of advanced penile cancer are disappointing, complete dissection of all involved lymph nodes is highly recommended. The extent of lymph node dissection should be adapted to clinical stage, as this corresponds to metastatic spread. For low-risk patients (pTis, pTa, and pT1G1) without palpable lymph nodes and with good compliance, a surveillance strategy may be chosen. For all other patients without palpable lymph nodes (including intermediate risk pT1G2 disease), a modified bilateral lymphadenectomy is recommended. An alternative to this is a dynamic sentinel lymph node biopsy in specialised centres. All patients with histologically proven lymph node metastases should undergo radical inguinal lymphadenectomy. Pelvic lymph node dissection should be done in all patients with more than two metastatic inguinal lymph nodes. In case of fixed inguinal lymph nodes, neoadjuvant chemotherapy is recommended, followed by node resection. Conclusions Lymphadenectomy is an integral part of the management of penile cancer, since early dissection of involved lymph nodes improves survival.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the intracellular lipid accumulation in hepatocytes. Excess caloric intake and high-fat diets are considered to ...significantly contribute to MASLD development.
To evaluate the hepatic and serum fatty acid (FA) composition in patients with different stages of MASLD, and their relationship with FA dietary intake and MASLD-related risk factors.
This was a case-control study in patients with obesity undergoing bariatric surgery at a University Hospital between January 2020 and December 2021. Participants were distributed in three groups: no MASLD (n = 26), steatotic liver disease (n = 33), and metabolic dysfunction-associated steatohepatitis (n = 32). Hepatic and serum FAs levels were determined by GC-MS. The nutritional status was evaluated using validated food frequency questionnaires. The hepatic expression of genes involved in FA metabolism was analyzed by RT-qPCR.
The hepatic, but not serum, FA profiles were significantly altered in patients with MASLD compared to those without MASLD. No differences were observed in FA intake between the groups. Levels of C16:0, C18:1, and the C18:1/C18:0 ratio were higher, while C18:0 levels and C18:0/C16:0 ratio were lower in patients with MASLD being significantly different between the three groups. Hepatic FA levels and ratios correlated with histopathological diagnosis and other MASLD-related parameters. The expression of genes involved in the FA metabolism was upregulated in patients with MASLD.
Alterations in hepatic FA levels in MASLD patients were due to an enhancement of the de novo lipogenesis in the liver.
The development and influence of physical capabilities and game action performance over the course of the season are a big challenge for coaches and players.
The aims of the present study were to ...examine (1) the seasonal changes in the physical capabilities (mechanical and kinematic) and game-performance indicators in top-level men volleyball players and (2) the relationship between these physical capabilities and game-performance indicators in official matches.
Eleven top-level players participated. Players were physically tested 3 times during the season. Before each test, players' match performance (11 sets) was analyzed according to the level of opposition and match location. The percentage of change, statistical differences over the season (Friedman and Wilcoxon tests), and associations between variables (Spearman r) were calculated (P < .05) among mechanical (force-velocity profile during vertical jump and bench press), kinematic (jump height and spike ball speed), and game action performance features (coefficient, efficacy, and percentage of errors in serve, attack, and block).
The theoretical maximal force and velocity during vertical jump and bench press, respectively; the peak spike ball speed; and the serve efficacy significantly increased over the season. Moreover, there was a significant reduction in serve errors as the jump height increased (r = -.44; P = .026), as well as a significant increase in serve errors as the peak spike ball speed increased (r = -.62; P = .001).
These findings reveal how the physical and game action performance variables evolve and interact during the season. This may help coaches and trainers to monitor and analyze the most relevant volleyball performance factors.
Circulating tumor DNA (ctDNA) has recently emerged as a real-time prognostic and predictive biomarker for monitoring cancer patients. Here, we aimed to ascertain whether tumor-agnostic ctDNA testing ...would be a feasible strategy to monitor disease progression and therapeutic response in muscle-invasive bladder cancer (MIBC) patients after radical cystectomy (RC). Forty-two MIBC patients who underwent RC were prospectively included. Blood samples from these patients were collected at different follow-up time points. Two specific mutations (
c.1-124C>T and
c.1236-2A>T) were analyzed in the patients' plasma samples by droplet digital PCR to determine their ctDNA status. During a median follow-up of 21 months, 24% of patients progressed in a median of six months. ctDNA status was identified as a prognostic biomarker of tumor progression before RC and 4 and 12 months later (HR 6.774, HR 3.673, and HR 30.865, respectively;
< 0.05). Lastly, dynamic changes in ctDNA status between baseline and four months later were significantly associated with patient outcomes (
= 0.045). In conclusion, longitudinal ctDNA analysis using a tumor-agnostic approach is a potential tool for monitoring MIBC patients after RC. The implementation of this testing in a clinical setting could improve disease management and patients' outcomes.
Abstract The exponential growth of novel therapies for the treatment of metastatic castration-resistant prostate cancer (mCRPC) over the last decade has created an acute need for education and ...guidance of clinicians regarding optimal strategies for patient management. A multidisciplinary panel of 21 European experts in mCRPC assembled for comprehensive discussion and consensus development, seeking to move the field forward and provide guidance and perspectives on optimal selection and sequencing of therapeutic agents and monitoring of response to treatment and disease progression. A total of 110 clinically-relevant questions were addressed and a modified Delphi method was utilised to obtain a consensus. The panel reached a consensus on several important issues, providing recommendations on appropriate phase III clinical trial end-points and optimal strategies for imaging and monitoring of bone metastases. Guidance regarding selection and sequencing of therapy in patients with newly diagnosed or progressive mCRPC is emphasised, including the use of novel bone-targeted agents, chemotherapy, androgen receptor pathway-targeted agents and immunotherapy. The impact of drug resistance and prostate-specific antigen flare on treatment decisions was also addressed. Ultimately, individualised therapy for patients with mCRPC is dependent on continued refinement of clinical decision-making based on patient and disease characteristics. This consensus statement offers clinicians expert guidance on the implementation of recent advances to improve patient outcome, focusing on the future of prostate cancer care.
PDF