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E-cigarettes (E.cigs) cause inflammation and damage to human organs, including the lungs and heart. In the gut, E.cig vaping promotes inflammation and gut leakiness. Further, E.cig vaping increases tumorigenesis in oral and lung epithelial cells by inducing mutations and suppressing host DNA repair enzymes. It is well known that cigarette (cig) smoking increases the risk of colorectal cancer (CRC). To date, it is unknown whether E.cig vaping impacts CRC development. A mouse model of human familial adenomatous polyposis (CPC-APC) was utilized wherein a mutation in the adenomatous polyposis coli (APC) gene, CDX2-Cre-APC Min/+ , leads to the development of colon adenomas within 11-16 weeks. Mice were exposed to air (controls), E.cig vaping, cig, or both (dual exposure). After 4 weeks of 2 h exposures per day (1 h of each for dual exposures), the colon was collected and assessed for polyp number and pathology scores by microscopy. Expression of inflammatory cytokines and cancer stem cell markers were quantified. DNA damage such as double-strand DNA breaks was evaluated by immunofluorescence, western blot, and gene-specific long amplicon qPCR. DNA repair enzyme levels (NEIL-2, NEIL-1, NTH1, and OGG1) were quantified by western blot. Proliferation markers were assessed by RT-qPCR and ELISA. CPC-APC mice exposed to E.cig, cig, and dual exposure developed a higher number of polyps compared to controls. Inflammatory proteins, DNA damage, and cancer stemness markers were higher in E-cig, cig, and dual-exposed mice as well. DNA damage was found to be associated with the suppression of DNA glycosylases, particularly with NEIL-2 and NTH1. E.cig and dual exposure both stimulated cancer cell stem markers (CD44, Lgr-5, DCLK1, and Ki67). The effect of E.cigs on polyp formation and CRC development was less than that of cigs, while dual exposure was more tumorigenic than either of the inhalants alone. E.cig vaping promotes CRC by stimulating inflammatory pathways, mediating DNA damage, and upregulating transcription of cancer stem cell markers. Critically, combining E.cig vaping with cig smoking leads to higher levels of tumorigenesis. Thus, while the chemical composition of these two inhalants, E.cigs and cigs, is highly disparate, they both drive the development of cancer and when combined, a highly common pattern of use, they can have additive or synergistic effects., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interest. Ethical approval: The manuscript includes animal experiments. The experimental design was approved by the University of California San Diego Institutional Animal Care and Use Committee (IACUC) policies under the animal protocol number (S18086 and S16021). No human data in this study., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Blastocystis is an anaerobic parasite that colonizes the intestinal tract of humans and animals. When it was first discovered, Blastocystis was considered to be a normal flora with beneficial effects on human health, such as maintaining gut hemostasis and improving intestinal barrier integrity. Later, with increasing research on Blastocystis , reports showed that Blastocystis sp. is associated with gastrointestinal disorders, colorectal cancer (CRC), and neurological disorders. The association between Blastocystis sp. and CRC has been confirmed in several countries. Blastocystis sp. can mediate CRC via similar mechanisms to CRC-associated bacteria, including infection-mediated inflammation, increased oxidative stress, induced gut dysbiosis, and damage to intestinal integrity, leading to a leaky gut. IL-8 is the main inflammatory cytokine released from epithelial cells and can promote CRC development. The causal association of Blastocystis sp. with other diseases needs further investigation. In this review, we have provided an update on Blastocystis sp. and summarized the debate about the beneficial and harmful effects of this parasite. We have also highlighted the possible mechanisms of Blastocystis -mediated CRC.

Background: E-cigarettes (E.cigs) cause inflammation and damage to human organs, including the lungs and heart. In the gut, E.cig vaping promotes inflammation and gut leakiness. Further, E.cig vaping increases tumorigenesis in oral and lung epithelial cells by inducing mutations and suppressing host DNA repair enzymes. It is well known that cigarette (cig) smoking increases the risk of colorectal cancer (CRC). To date, it is unknown whether E.cig vaping impacts CRC development., Methods: A mouse model of human familial adenomatous polyposis (CPC-APC) was utilized wherein a mutation in the adenomatous polyposis coli (APC) gene, CDX2-Cre-APC Min/+ , leads to the development of colon adenomas within 16 weeks. Mice were exposed to air (controls), E.cig vaping, cig, or both (dual exposure). After 4 weeks of 2-hour exposures per day (1 hour of each for dual exposures), the colon was collected and assessed for polyp number and pathology scores by microscopy. Expression of inflammatory cytokines and cancer stem cell markers were quantified. DNA damage such as double-strand DNA breaks was evaluated by immunofluorescence, western blot and gene-specific long amplicon qPCR. DNA repair enzyme levels (NEIL-2, NEIL-1, NTH1, and OGG1) were quantified by western blot. Proliferation markers were assessed by RT-qPCR and ELISA., Results: CPC-APC mice exposed to E.cig, cig, and dual exposure developed a higher number of polyps compared to controls. Inflammatory proteins, DNA damage, and cancer stemness markers were higher in E-cig, cig, and dual-exposed mice as well. DNA damage was found to be associated with the suppression of DNA glycosylases, particularly with NEIL-2 and NTH1. E.cig and dual exposure both stimulated cancer cell stem markers ( CD44 , Lgr-5, DCLK1, and Ki67) . The effect of E.cigs on polyp formation and CRC development was less than that of cigs, while dual exposure was more tumorigenic than either of the inhalants alone., Conclusion: E.cig vaping promotes CRC by stimulating inflammatory pathways, mediating DNA damage, and upregulating transcription of cancer stem cell markers. Critically, combining E.cig vaping with cig smoking leads to higher levels of tumorigenesis. Thus, while the chemical composition of these two inhalants, E.cigs and cigs, is highly disparate, they both drive the development of cancer and when combined, a highly common pattern of use, they can have additive or synergistic effects., Competing Interests: Competing interest: The authors declare no competing interest.

Objective and Design: Annexin A1 (ANXA1) plays a role in maintaining intestinal hemostasis, especially following mucosal inflammation. The published data about ANXA1 was derived from experimental animal models where there is an overlapping between epithelial and immune cells. There is no in vitro gut epithelial model that can assess the direct effect of ANXA1 on the gut epithelium., Methods: We developed high-throughput stem-cell-based murine epithelial cells and bacterial lipopolysaccharides (LPS) were used to induce inflammation. The impact of ANXA1 and its functional part (Ac2-26) was evaluated in the inflamed model. Intestinal integrity was assessed by the transepithelial electrical resistance (TEER), and FITC-Dextran permeability. Epithelial junction proteins were assessed using confocal microscopy and RT-qPCR. Inflammatory cytokines were evaluated by RT-qPCR and ELISA., Results: LPS challenge mediated a damage in the epithelial cells as shown by a drop in the TEER and an increase in FITC-dextran permeability; reduced the expression of epithelial junctional proteins (Occludin, ZO-1, and Cadherin) and increased the expression of the gut leaky protein, Claudin - 2. ANXA1 and Ac2-26 treatment reduced the previous damaging effects. In addition, ANXA1 and Ac2-26 inhibited the inflammatory responses mediated by the LPS and increased the transcription of the anti-inflammatory cytokine, IL-10., Conclusion: ANXA1 and Ac2-26 directly protect the epithelial integrity by affecting the expression of epithelial junction and inflammatory markers. The inflamed gut model is a reliable tool to study intestinal inflammatory diseases, and to evaluate the efficacy of potential anti-inflammatory drugs and the screening of new drugs that could be candidates for inflammatory bowel disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The host EnguLfment and cell MOtility protein 1 (ELMO1) is a cytosolic microbial sensor that facilitates bacterial sensing, internalization, clearance, and inflammatory responses. We have shown previously that ELMO1 binds bacterial effector proteins, including pathogenic effectors from Salmonella and controls host innate immune signaling. To understand the ELMO1-regulated host pathways, we have performed liquid chromatography Multinotch MS3-Tandem Mass Tag (TMT) multiplexed proteomics to determine the global quantification of proteins regulated by ELMO1 in macrophages during Salmonella infection. Comparative proteome analysis of control and ELMO1-depleted murine J774 macrophages after Salmonella infection quantified more than 7000 proteins with a notable enrichment in mitochondrial-related proteins. Gene ontology enrichment analysis revealed 19 upregulated and 11 downregulated proteins exclusive to ELMO1-depleted cells during infection, belonging to mitochondrial functions, metabolism, vesicle transport, and the immune system. By assessing the cellular energetics via Seahorse analysis, we found that Salmonella infection alters mitochondrial metabolism, shifting it from oxidative phosphorylation to glycolysis. Importantly, these metabolic changes are significantly influenced by the depletion of ELMO1. Furthermore, ELMO1 depletion resulted in a decreased ATP rate index following Salmonella infection, indicating its importance in counteracting the effects of Salmonella on immunometabolism. Among the proteins involved in mitochondrial pathways, mitochondrial fission protein DRP1 was significantly upregulated in ELMO1-depleted cells and in ELMO1-KO mice intestine following Salmonella infection. Pharmacological Inhibition of DRP1 revealed the link of the ELMO1-DRP1 pathway in regulating the pro-inflammatory cytokine TNF-α following infection. The role of ELMO1 has been further characterized by a proteome profile of ELMO1-depleted macrophage infected with SifA mutant and showed the involvement of ELMO1-SifA on mitochondrial function, metabolism and host immune/defense responses. Collectively, these findings unveil a novel role for ELMO1 in modulating mitochondrial functions, potentially pivotal in modulating inflammatory responses., Significance Statement: Host microbial sensing is critical in infection and inflammation. Among these sensors, ELMO1 has emerged as a key regulator, finely tuning innate immune signaling and discriminating between pathogenic and non-pathogenic bacteria through interactions with microbial effectors like SifA of Salmonella . In this study, we employed Multinotch MS3-Tandem Mass Tag (TMT) multiplexed proteomics to determine the proteome alterations mediated by ELMO1 in macrophages following WT and SifA mutant Salmonella infection. Our findings highlight a substantial enrichment of host proteins associated with metabolic pathways and mitochondrial functions. Notably, we validated the mitochondrial fission protein DRP1 that is upregulated in ELMO1-depleted macrophages and in ELMO1 knockout mice intestine after infection. Furthermore, we demonstrated that Salmonella -induced changes in cellular energetics are influenced by the presence of ELMO1. This work shed light on a possible novel link between mitochondrial dynamics and microbial sensing in modulating immune responses.

Viral infections trigger inflammation by controlling ATP release. CD39 ectoenzymes hydrolyze ATP/ADP to AMP, which is converted by CD73 into anti-inflammatory adenosine (ADO). ADO is an anti-inflammatory and immunosuppressant molecule which can enhance viral persistence and severity. The CD39-CD73-adenosine axis contributes to the immunosuppressive T-reg microenvironment and may affect COVID-19 disease progression. Here, we investigated the link between CD39 expression, mostly on T-regs, and levels of CD73, adenosine, and adenosine receptors with COVID-19 severity and progression. Our study included 73 hospitalized COVID-19 patients, of which 33 were moderately affected and 40 suffered from severe infection. A flow cytometric analysis was used to analyze the frequency of T-regulatory cells (T-regs), CD39+ T-regs, and CD39+CD4+ T-cells. Plasma concentrations of adenosine, IL-10, and TGF-β were quantified via an ELISA. An RT-qPCR was used to analyze the gene expression of CD73 and adenosine receptors (A1, A2A, A2B, and A3). T-reg cells were higher in COVID-19 patients compared to healthy controls (7.4 ± 0.79 vs. 2.4 ± 0.28; p < 0.0001). Patients also had a higher frequency of the CD39+ T-reg subset. In addition, patients who suffered from a severe form of the disease had higher CD39+ T-regs compared with moderately infected patients. CD39+CD4+ T cells were increased in patients compared to the control group. An analysis of serum adenosine levels showed a marked decrease in their levels in patients, particularly those suffering from severe illness. However, this was paralleled with a marked decline in the expression levels of CD73. IL-10 and TGF-β levels were higher in COVID-19; in addition, their values were also higher in the severe group. In conclusion, there are distinct immunological alterations in CD39+ lymphocyte subsets and a dysregulation in the adenosine signaling pathway in COVID-19 patients which may contribute to immune dysfunction and disease progression. Understanding these immunological alterations in the different immune cell subsets and adenosine signaling provides valuable insights into the pathogenesis of the disease and may contribute to the development of novel therapeutic approaches targeting specific immune mechanisms.

Background: Engulfment and cell motility protein 1 (ELMO1) is a key protein for innate immunity since it is required for the clearance of apoptotic cells and pathogenic bacteria as well as for the control of inflammatory responses. ELMO1, through binding with Dock180 and activation of the Rac1 signaling pathway, plays a significant role in cellular shaping and motility. Rac-mediated actin cytoskeletal rearrangement is essential for bacterial phagocytosis, but also plays a crucial role in processes such as cancer cell invasion and metastasis. While the role of ELMO1 in bacterial infection and inflammatory responses is well established, its implication in cancer is not widely explored yet. Molecular changes or epigenetic alterations such as DNA methylation, which ultimately leads to alterations in gene expression and deregulation of cellular signaling, has been reported for ELMO1 in different cancer types., Conclusions: In this review, we provide an updated and comprehensive summary of the roles of ELMO1 in infection, inflammatory diseases and cancer. We highlight the possible mechanisms regulated by ELMO1 that are relevant for cancer development and progression and provide insight into the possible use of ELMO1 as a diagnostic biomarker and therapeutic target., (© 2022. Springer Nature Switzerland AG.)

Searches for dark matter axions involve the use of microwave resonant cavities operating in a strong magnetic field. Detector sensitivity is directly related to the cavity quality factor, which is limited, until recently, to the use of non-superconducting metals by the presence of the external magnetic field. In this paper, we present a cavity of novel design whose quality factor is not affected by a magnetic field. It is based on a photonic structure by the use of sapphire rods. The quality factor at cryogenic temperature is in excess of 5 × 10 5 for a selected mode.

Protein arginine methyltransferase 5 (PRMT5) controls diverse cellular processes and is implicated in cancer development and progression. Here, we report an inverse correlation between PRMT5 function and antitumor immunity. PRMT5 expression was associated with an antitumor immune gene signature in human melanoma tissue. Reducing PRMT5 activity antagonized melanoma growth in immunocompetent but not immunocompromised mice. PRMT5 methylation of IFI16 [interferon-γ (IFN-γ)-inducible protein 16] or its murine homolog IFI204, which are components of the cGAS/STING (stimulator of IFN genes) pathway, attenuated cytosolic DNA-induced IFN and chemokine expression in melanoma cells. PRMT5 also inhibited transcription of the gene encoding NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5), a protein that promotes the expression of genes implicated in major histocompatibility complex class I (MHCI) antigen presentation. PRMT5 knockdown augmented IFN and chemokine production and increased MHCI abundance in melanoma. Increased expression of IFI204 and NLRC5 was associated with decreased melanoma growth in murine models, and increased expression of IFI16 and NLRC5 correlated with prolonged survival of patients with melanoma. Combination of pharmacological (GSK3326595) or genetic (shRNA) inhibition of PRMT5 with immune checkpoint therapy limited growth of murine melanoma tumors (B16F10 and YUMM1.7) and enhanced therapeutic efficacy, compared with the effect of either treatment alone. Overall, our findings provide a rationale to test PRMT5 inhibitors in immunotherapy-based clinical trials as a means to enhance an antitumor immune response., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: The standard treatment for hallux valgus in rheumatoid arthritis has been arthrodesis of the first metatarsophalangeal (MTP) joint. There is limited literature regarding the results of hallux valgus procedures which preserve the first MTP joint in rheumatoid patients. We investigated the radiographic and clinical outcomes of joint-preserving surgery for hallux valgus in a series of rheumatoid patients to evaluate the result of nonarthrodesis reconstruction., Methods: Thirty-seven feet with hallux valgus in 27 patients with RA treated with a joint-preserving procedure of the first MTP joint were analyzed radiographically and clinically. Average follow-up was 42 (range, 12-111) months. Twenty feet had Ludloff osteotomies, 15 had scarf osteotomies, and 2 had chevron osteotomies. Radiographs were evaluated preoperatively and postoperatively for hallux valgus angle, 1-2 intermetatarsal angle, and degenerative narrowing of the first MTP joint based the Sharp score and the Larsen grade. Narrowing of the first interphalangeal (IP) joint was based on a modification of the classification of Hattrup and Johnson. Operative complications and required secondary surgeries were tabulated. Clinical outcomes were measured using preoperative and postoperative Short Form-36 (SF-36), AOFAS forefoot scale, and Visual Analogue Scale (VAS) pain questionnaires., Results: The average hallux valgus angle improved from 37 degrees preoperatively to 15 degrees postoperatively. The average 1-2 intermetatarsal angle improved from 14 degrees preoperatively to 5 degrees postoperatively. The average Sharp score of the first MTP joint was 0.9 preoperatively and 1.6 postoperatively. The average Larsen grade of the first MTP joint was 0.6 preoperatively and 1.4 postoperatively. Range of motion of the first MTP joint was essentially unchanged between preoperative and postoperative measurements. Seven of 37 feet had progression of first IP joint space narrowing, but none were symptomatic. The AOFAS score improved from 45.2 preoperatively to 82.6 at final follow-up (P value < .01). The VAS decreased from 4.8 preoperatively to 1.5 at final follow-up (P value < .02). The SF-36 physical component score decreased from 40.3 preoperatively to 37.4 at final follow-up, and the mental component score remained unchanged, and neither was statistically significant. There were 7 feet (19%) that required a return to surgery: 3 wound infections, 2 arthrodeses for progression of deformity, and 1 each for revision for recurrence and hardware removal., Conclusion: Rheumatoid arthritis patients who undergo a bunionectomy rather than arthrodesis to preserve the first MTP joint have satisfactory clinical and radiographic outcomes. This procedure appeared to be a reasonable alternative to first MTP arthrodesis in patients with relatively preserved joints., Level of Evidence: Level IV, retrospective case series.

Prospective outcome studies are generally considered to be better than retrospective studies. The purpose of this study was to assess correlations between prospective and retrospective outcome assessment after rotator cuff repair. One-hundred and twelve patients (118 shoulders) with chronic rotator cuff tears were evaluated at a mean of 54 months (34-85) after rotator cuff repair, using several outcome measures including a retrospective assessment of improvement. The retrospective assessment of post-operative pain, function, and quality of life had fair correlations with the prospectively determined improvement (R = .23-.25, P < .01). Post-operative patient satisfaction was more highly correlated with all retrospective evaluations than with the prospective improvement in all functional outcome measures. Retrospective and prospective evaluations of the outcome of rotator cuff repair are different. Patient satisfaction has a greater correlation with retrospective outcomes. Retrospective evaluation may aid in supplementing prospective evaluations, as it may better reflect a patient's perception of the success after surgery.

A number of variables are used to assess the outcome of rotator cuff repair (RCR), including patient satisfaction. The purpose of this study was to determine the factors that affect patient satisfaction after RCR. The study assessed 112 patients (118 shoulders) with chronic rotator cuff tears preoperatively and at a mean of 54 months (range, 34-85 months) after RCR by using several functional outcome questionnaires and an evaluation of patient satisfaction. Of these, 95% were satisfied with the outcome of the surgery. Satisfaction was significantly correlated with the improvement in functional outcomes and general health status and absolute postoperative functional outcomes. Married, currently working, and nondisabled patients had greater satisfaction. High preoperative and postoperative met expectations were also positively correlated with patient satisfaction. Patient satisfaction is most highly correlated with the pain, function, and general health status of the patient after RCR. We conclude that aspects of treatment that maximize the functional outcome are important in achieving patient satisfaction after RCR.