[Understanding New Regulatory Mechanism of TCR Signal Transduction].

Signal-transducing adaptor protein-2 (STAP-2) is a unique scaffold protein that regulates several immunological signaling pathways, including LIF/LIF receptor and LPS/TLR4 signals. STAP-2 is required for Fas/FasL-dependent T cell apoptosis and SDF-1α-induced T cell migration. Conversely, STAP-2 modulates integrin-mediated T cell adhesion, suggesting that STAP-2 is essential for several negative and positive T cell functions. However, whether STAP-2 is involved in T cell-antigen receptor (TCR)-mediated T cell activation is unknown. STAP-2 deficiency was recently reported to suppress TCR-mediated T cell activation by inhibiting LCK-mediated CD3ζ and ZAP-70 activation. Using STAP-2 deficient mice, it was demonstrated that STAP-2 is required for the pathogenesis of Propionibacterium acnes-induced granuloma formation and experimental autoimmune encephalomyelitis. Here, detailed functions of STAP-2 in TCR-mediated T cell activation, and how STAP-2 affects the pathogenesis of T cell-mediated inflammation and immune diseases, are reviewed.

Cryopreserved bone flaps from decompressive craniectomies: a microbiological analysis.

PURPOSE: Surgical site infection (SSI) is a serious complication after cranioplasty. Due to the relatively frequent occurrence of post-cranioplasty SSI, the utility of autologous bone flap swab cultures surrounding cryopreservation as a reliable predictor has been the subject of an ongoing debate. This bicentric study aims to contribute to this topic by conducting an in-depth analysis of bone flaps obtained via decompressive craniectomies. This study had three major aims: assessments of 1) bacterial contamination of bone flaps after decompressive craniotomy, 2) impact of cryoconservation on contamination rates and 3) potential effectiveness of anti-infective treatment to reduce the germ load prior to cranioplasty. METHODS: Cryopreserved bone flaps from two centers were used. Microbiological cultivations of swabs prior to and after cryopreservation were taken and assessed for aerobic and anaerobic growth over a 14-day incubation period. Additionally, in a subset of bone flaps, swab testing was repeated after thorough rinsing with an anti-infectant (octenidine-phenoxyethanol) followed by saline. RESULTS: All 63 bone flaps (patients median age at surgery: 59 years) were obtained via decompressive craniectomies. Swabs done prior to cryopreservation revealed a 54% infection rate with Propionibacterium acnes being the most common microorganism in 65% of those cases. After thorough disinfection of the preserved bone flaps, all but one case showed no bacterial growth in swab testing. Furthermore, no relevant risk factors for bacterial contamination could be identified. CONCLUSION: This retrospective study showed the common presence of bacterial growth in cryopreserved bone flaps before and after freezing. Rinsing with octenidine-phenoxyethanol and saline effectively prevented bacterial growth in a notable percentage of cases, suggesting a potential strategy to reduce contamination. However, persistent bacterial growth in some cases underscores the need for further research to optimize antiseptic measures during autologous cranioplasty.

Investigation into the Anti-Acne Effects of Castanea sativa Mill Leaf and Its Pure Ellagitannin Castalagin in HaCaT Cells Infected with Cutibacterium acnes.

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 µg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin's bioactivity mirrored the extract's effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low µM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract's biological activities. This study is the first to explore ellagitannins' potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.

The effect of different antibiotic combinations in calcium sulfate cement on the growth of Cutibacterium acnes and Staphylococcus periprosthetic shoulder infection isolates.

BACKGROUND: Periprosthetic joint infections (PJI) of the shoulder are a devastating complication of shoulder arthroplasty and are commonly caused by Staphylococcus and Cutibacterium acnes. Absorbable calcium sulfate (CS) beads are sometimes used for delivering antibiotics in PJI. This study evaluates the in vitro effect of different combinations of gentamicin, vancomycin, and ertapenem in beads made from CS cement on the growth of C acnes and coagulase-negative Staphylococcus (CNS) strains. METHODS: Three strains of C acnes and 5 strains of CNS from clinically proven shoulder PJI were cultured and plated with CS beads containing combinations of vancomycin, gentamicin, and ertapenem. Plates with C acnes were incubated anaerobically while plates with Staphylococcus were incubated aerobically at 37 °C. Zones of inhibition were measured at intervals of 3 and 7 days using a modified Kirby Bauer technique, and beads were moved to plates containing freshly streaked bacteria every seventh day. This process was run in triplicate over the course of 56 days. Statistical analysis was conducted using SPSS v. 28 with repeated measures analysis of variance (ANOVA) and pairwise comparisons with Tukey correction. RESULTS: In experiments with C acnes, beads containing ertapenem + vancomycin and vancomycin alone formed the largest zones of inhibition over time (P < .001). In experiments with Staphylococcus, beads containing vancomycin alone formed the largest zones of inhibition over time for all 5 strains (P < .001). Zones of inhibition were 1.4x larger for C acnes than for Staphylococcus with beads containing vancomycin alone. For both C acnes and Staphylococcus, beads containing ertapenem had the strongest initial effect, preventing all bacterial growth in C acnes and almost all growth for Staphylococcus during the first week but dropping substantially by the second week. Beads containing gentamicin alone consistently created smaller zones of inhibition than beads containing vancomycin alone, with vancomycin producing zones 5.3x larger than gentamicin in C acnes and 1.3x larger in Staphylococcus (P < .001). DISCUSSION: These data suggest that for both C acnes and Staphylococcal species, CS beads impregnated with vancomycin were most effective at producing a robust antibiotic effect. Additionally, ertapenem may be a viable supplement in order to create a more potent initial antibiotic effect but is not as effective as vancomycin when used alone. Gentamicin alone was not effective in maintaining consistent and long-term antibiotic effects. These results indicate that amongst the antibiotics currently commercially available to be used with CS, vancomycin is consistently superior to gentamicin in the setting of C. acnes and CNS.

Risk factors associated with low-grade virulent infection in intervertebral disc degeneration: a systematic review and meta-analysis.

BACKGROUND: An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD. PURPOSE: This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut. RESULTS: Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD. CONCLUSIONS: Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age.

Application of bacteriophage φPaP11-13 attenuates rat Cutibacterium acnes infection lesions by promoting keratinocytes apoptosis via inhibiting PI3K/Akt pathway.

Acne vulgaris caused by antibiotic-resistant Cutibacterium acnes (C. acnes) infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the mechanism of phage treatment is inadequate. This research investigates the underlying molecular mechanisms of phage φPaP11-13 attenuating C. acnes-induced inflammation in rat models. We found that rats infected with C. acnes had higher average ear thickness, greater enrichment of inflammatory cells as shown by hematoxylin-eosin (HE) staining, and fewer TUNEL (TdT-mediated dUTP Nick-End Labeling)-positive keratinocytes visualized by IF staining. Moreover, an increase of IGF-1 and IGF-1 receptor (IGF-1r) was detected using the immunohistochemical (IHC) staining method, Western blot (WB), and quantitative real-time PCR (qRT-PCR) when infected with C. acnes, which was decreased after the application of phage φPaP11-13. By applying the IGF-1 antibody, it was demonstrated that the severity of C. acnes-induced inflammation was relevant to the expression of IGF-1. Through WB and qRT-PCR, activation of the PI3K/Akt pathway and a down-regulation of the BAD-mediated apoptosis pathway were discovered after C. acnes infection. Subsequently, it was shown that the activation of the PI3K/Akt pathway against BAD-mediated apoptosis pathway was alleviated after applying phage φPaP11-13. Furthermore, applying the IGF-1r inhibitor, Pan-PI3K inhibitor, and Akt inhibitor reversed the changing trends of BAD induced by C. acnes and phage φPaP11-13. This study demonstrates that one of the critical mechanisms underlying the attenuation of acne vulgaris by phage φPaP11-13 is lysing C. acnes and regulating keratinocyte apoptosis via the PI3K/Akt signaling pathway.IMPORTANCECutibacterium acnes infection-induced acne vulgaris may cause severe physical and psychological prognosis. However, the overuse of antibiotics develops drug resistance, bringing challenges in treating Cutibacterium acnes. Bacteriophages are currently proven effective in MDR (multiple drug-resistant) Cutibacterium acnes, but there is a significant lack of understanding of phage therapy. This study demonstrated a novel way of curing acne vulgaris by using phages through promoting cell death of excessive keratinocytes in acne lesions by lysing Cutibacterium acnes. However, the regulation of this cell cycle has not been proven to be directly mediated by phages. The hint of ternary relation among "phage-bacteria-host" inspires huge interest in future phage therapy studies.

The incidence of subclinical infection in patients undergoing revision shoulder stabilization surgery: a retrospective chart review.

BACKGROUND: Shoulder instability continues to be a common problem that is difficult to treat. Part of this difficulty can be attributed to the numerous postoperative complications that can impact the clinical course. Our study aims to primarily identify the incidence of subclinical infection in patients undergoing revision shoulder stabilization surgery and secondarily identify any risk factors for developing a subclinical infection. MATERIALS AND METHODS: From January 2012 to December 2022, 94 charts of patients who underwent revision surgery by the senior author after a previous arthroscopic or open stabilization surgery for shoulder instability were reviewed. All patients of any age who underwent either bony or soft tissue revision surgery, regardless of the number of previous surgeries or corticosteroid injections, were included. Patients were excluded if they had a previous infection in the shoulder, if there was no record of the procedures performed in the previous surgery, or if cultures were not available for review. For each patient, demographic information (age, sex, race, smoking status, previous corticosteroid injections, malnutrition, renal failure, liver failure, diabetes mellitus, immunocompromised status, and intravenous drug use), surgical information (procedures performed, type of surgery, and date of surgery), and culture results were recorded. RESULTS: Overall, 107 patients were included in our study. Twenty-nine patients (27.1%) had positive cultures (60 cultures in total). Twenty-six patients had positive Cutibacterium acnes (C. acnes) cultures. On average, C. acnes cultures took 10.65 days to turn positive, whereas 24 of 27 patients had cultures that were positive within 14 days of the culture being obtained. There was no difference in infection incidence rates between soft tissue and bony stabilization procedures (P = .86) or arthroscopic and open procedures (P = .59). Males were more than 5 times more likely than females to be culture positive in our cohort (93.1% vs. 73.1%, relative risk [RR] = 1.27, P = .03). Finally, 10 control cultures were taken from the operating room air environment (8 distinct surgeries had 1 control culture taken, whereas 1 surgery had 2), 2 of which were positive for C. acnes (both taken from the same patient operation). This patient had their shoulder cultures positive for C. acnes as well. CONCLUSION: More than a quarter of patients requiring revision surgery after shoulder stabilization procedures have a subclinical shoulder infection, with males being at a higher risk of developing an infection than females. Surgeons should always consider infection as a reason for the lack of clinical improvement and possibly needing revision surgery after shoulder stabilization. The prompt diagnosis and treatment of these infections could be vital in improving results after these surgeries.

Sarcoidosis Associated with Enlarged Mediastinal Lymph Nodes with the Detection of Streptococcus gordonii and Cutibacterium acnes Using a Clone Library Method.

A 77-year-old Japanese woman with mediastinal lymphadenopathy and uveitis was diagnosed with sarcoidosis. The bacterial flora in biopsied samples from mediastinal lymph nodes was analyzed using a clone library method with Sanger sequencing of the 16S rRNA gene, and Streptococcus gordonii (52 of 71 clones) and Cutibacterium acnes (19 of 71 clones) were detected. No previous study has conducted a bacterial floral analysis using the Sanger method for the mediastinal lymph node in sarcoidosis, making this case report the first to document the presence of S. gordonii and C. acnes in the mediastinal lymph node of a patient with sarcoidosis.

Does hydrogen peroxide application to the dermis following surgical incision affect Cutibacterium acnes cultures in total shoulder arthroplasty in male patients? A randomized controlled trial.

BACKGROUND: Periprosthetic joint infections occur in 1%-4% of primary total shoulder arthroplasties (TSAs). Cutibacterium acnes is the most commonly implicated organism and has been shown to persist in the dermis despite use of preoperative antibiotics and standard skin preparations. Studies have shown decreased rates of cultures positive for C acnes with use of preoperative benzoyl peroxide or hydrogen peroxide (H2O2), but even with this positive deep cultures remain common. We sought to determine whether an additional application of H2O2 directly to the dermis following skin incision would further decrease deep culture positivity rates. METHODS: We performed a randomized controlled trial comparing tissue culture results in primary TSA in patients who received a standard skin preparation with H2O2, ethanol, and ChloraPrep (CareFusion, Leawood, KS, USA) vs. an additional application of H2O2 to the dermis immediately after skin incision. Given the sexual dimorphism seen in the shoulder microbiome regarding C acnes colonization rates, only male patients were included. Bivariable and multivariable analyses were performed to compare rates of positive cultures based on demographic and surgical factors. RESULTS: Dermal cultures were found to be positive for C acnes at similar rates between the experimental and control cohorts for the initial (22% vs. 28%, P = .600) and final (61% vs. 50%, P > .999) dermal swabs. On bivariable analysis, the rate of positive deep cultures for C acnes was lower in the experimental group, but this difference was not statistically significant (28% vs. 44%, P = .130). However, patients who underwent anatomic TSA were found to have a significantly greater rate of deep cultures positive for C acnes (57% vs. 28%, P = .048); when controlling for this on multivariable analysis, the experimental cohort was found to be associated with significantly lower odds of having positive deep cultures (odds ratio, 0.37 [95% confidence interval, 0.16-0.90], P = .023). There were no wound complications in either cohort. CONCLUSIONS: An additional H2O2 application directly to the dermis following skin incision resulted in a small but statistically significant decrease in the odds of having deep cultures positive for C acnes without any obvious adverse effects on wound healing. Given its cost-effectiveness, use of a post-incisional dermal decontamination protocol may be considered as an adjuvant to preoperative use of benzoyl peroxide or H2O2 to decrease C acnes contamination.

Detection of Cutibacterium (Propionibacterium) acnes in orthopaedic surgery: serious problem or contamination?

PURPOSE: Bone and joint infections are an important and increasing problem. Whether intraoperatively detected bacteria should be considered relevant or not is often difficult to assess. This retrospective cohort study analyzes the relevance of C. acnes cultured from deep intraoperative specimens. METHODS: All deep tissue samples collected intraoperatively between 2015 and 2020 from a quartiary care provider were evaluated for detection of C. acnes and its therapeutical consequences. Infection rates were determined according to a standardized definition and protocol and analyzed in dependence of patient's demographic data (age and gender), operative parameters (type of surgery, body region/location of surgery, and impression of the surgeon), and initiated therapy. RESULTS: In 270 cases of more than 8500 samples, C. acnes was detected. In 30%, the detection was considered an infection. The number of samples taken and tested positive for C. acnes correlated significantly with its classification as a cause of infection. If more than one sample of the patient was positive, the detection was significantly more likely to be treated as infection (p < 0.001). In 76% of cases, a consultation to the infectious diseases (ID) department took place regarding the classification of the pathogen detection and the therapy to be carried out. Almost all of the tested isolates demonstrated the wild-type susceptibility for penicillin and clindamycin. CONCLUSION: Intraoperative detection of skin-colonizing bacteria such as C. acnes is not always synonymous with infection. In particular, if other examination results contradict an infection (pathological sample without evidence of an infectious event, detection of malignant cells, etc.), the situation must be considered in a very differentiated manner. Interdisciplinary boards, for example, are suitable for this purpose. Care should be taken to obtain a sufficiently large number of tissue samples for microbiological examination to be able to better classify the result.

Are Cutibacterium acnes delivered from skin to deep tissues in primary reverse shoulder arthroplasty? A prospective study.

INTRODUCTION: The objective of this study is to determine whether the deep tissues are inoculated during surgery with the Cutibacterium acnes still present in the skin after the surgical preparation in reverse shoulder arthroplasties. MATERIALS AND METHODS: Prospective study including patients undergoing surgery with reverse shoulder arthroplasty. All the patients received preoperative antibiotic prophylaxis with cefazolin (2 g IV) and the skin was prepared with 2% chlorhexidine gluconate and 70% isopropyl alcohol. From all the patients, 9 cultures were obtained after the antibiotic was administrated and the skin surgically prepared. The cultures were sent to isolate C. acnes. DNA was extracted from the C. acnes isolated colonies. Isolate nucleotide distances were calculated using the Genome-based distance matrix calculator from the Enveomics collection toolbox. RESULTS: The study included 90 patients. C. acnes was isolated in 24 patients (26.6%) with a total of 61 positive cultures. There were 12 phylotype II, 27 IB and 22 IA. In 9 patients, C. acnes was present in both skin and deep tissues, and they constituted the sample to be studied by means of genomic analysis. In 7 out of the 9 patients, deep tissue samples clustered closer to at least one of its corresponding skin isolates when compared to the other independent bacterial ones. CONCLUSIONS: The C. acnes present in the skin at the beginning of the surgery are the same as those found in the deep tissues at the end of the surgery. This result strengthens the possibility that the C. acnes is delivered from the skin to the deep tissues.

Effect of making skin incision with electrocautery on positive Cutibacterium acnes culture rates in shoulder arthroplasty: a prospective randomized clinical trial.

BACKGROUND: Cutibacterium acnes remains the most commonly detected organism in shoulder arthroplasty. C acnes infection is thought to occur during shoulder arthroplasty through contamination of the surgical field with C acnes from the incised dermis. The purpose of this study was to examine whether using electrocautery for making skin incisions would decrease C acnes culture rates at the incised dermis compared to using scalpels during shoulder arthroplasty. METHODS: Patients undergoing primary shoulder arthroplasty were randomized into 2 groups, electrocautery vs. scalpel incision group. All patients received a standard preoperative antiseptic preparation including chlorhexidine gluconate showers, intravenous antibiotic administration, and topical application of hydrogen peroxide, povidone iodine, isopropyl alcohol, and DuraPrep. Cultures were obtained from the incised dermal edge immediately after skin incision and later from surgeon's gloves and forceps immediately prior to humeral component implantation. The primary outcome was positive C acnes culture rates compared between the groups. RESULTS: A total of 64 patients (32 in each group) were enrolled. There were 24 males in each group. Regarding dermis cultures, 10 patients (31%) in the scalpel group were positive with 8 of them positive for C acnes, whereas no patients in the electrocautery group were positive (P < .001). Regarding glove cultures, the electrocautery group had 8 patients positive C acnes, while the scalpel group had 8 (P = .777). Regarding forceps cultures, the electrocautery group had 4 patients positive for C acnes, and the scalpel group had 6 (P = .491). All positive cultures were exclusively from male patients. There were no wound complications or infection in the electrocautery group while the scalpel group had 1 acute postoperative infection. CONCLUSIONS: Making skin incisions using electrocautery resulted in 0 C acnes culture at the incised dermis, suggesting its potential effect against C acnes. However, despite this initial antibacterial effect, C acnes still appeared on surgeon's gloves and forceps during surgery of male patients. All positive cultures were from male patients, suggesting that the source of C acnes was specifically related to the male body. While the study hypothesis was supported by the results, the present study also raises new questions and calls for further research.

Tumor-isolated Cutibacterium acnes as an effective tumor suppressive living drug.

The two major challenges in cancer treatment are reducing the side effects and minimizing the cost of cancer treatment. A better therapy to treat cancer remains to be developed despite the presence of many therapeutic options. Here, we present bacterial therapy for treating cancer using tumor-isolated Cutibacterium acnes, which is safe to use, has minimal side effects compared to chemotherapeutic drugs, and most importantly, targets the tumor microenvironment due to the bacterium's anaerobic nature. It activates the immune system, and the immune cells effectively penetrate through the tumor tissue and form an immunologic hub inside, explicitly targeting the tumor and destroying the cells. This bacterial therapy is a new cost-effective innovative treatment.

Dyslipidaemia is associated with Cutibacterium acnes hip and knee prosthetic joint infection.

PURPOSE: Optimization of medical factors including diabetes and obesity is a cornerstone in the prevention of prosthetic joint infection (PJI). Dyslipidaemia is another component of metabolic syndrome which has not been thoroughly investigated as an individual, modifiable risk factor. This study examined the association of dyslipidaemia with PJI caused by the lipophilic microbe Cutibacterium acnes (C. acnes). METHODS: A retrospective chart review examined patients with positive C. acnes culture at hip or knee arthroplasty explantation. A control group with methicillin-sensitive Staphylococcus aureus (MSSA) positive cultures at explantation was matched for age, sex, and surgical site, as well as a second control group with no infection. A total of 80 patients were included, 16 with C. acnes, 32 with MSSA, and 32 with no infection. All patients had a lipid panel performed within one year of surgery. Lipid values and categories were compared using multinomial logistic regressions. RESULTS: High or borderline triglycerides (TG) (relative risk ratio (RRR) = 0.13; P = 0.013) and low high-density lipoprotein (HDL) (RRR = 0.13; P = 0.025) were significantly associated with C. acnes PJI compared to MSSA-PJI. High or borderline TG (RRR = 0.21; P = 0.041) and low HDL (RRR = 0.17; P = 0.043) were also associated with a greater probability of C. acnes infection compared to no infection. CONCLUSIONS: The presence of elevated TG and low HDL were both associated at a statistically significant level with C. acnes hip or knee PJI compared to controls with either MSSA PJI or no infection. This may represent a specific risk factor for C. acnes PJI that is modifiable.

Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.

Cryptosporidium parvum is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom Cryptosporidium treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with Cryptosporidium parvum of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that C. parvum infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic C. parvum infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic Cryptosporidium infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.

Association of Cutibacterium acnes with human thyroid cancer.

Introduction: The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer. Methods: We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer. Results: Our analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer. Conclusion: Cutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.

Viaminate Inhibits Propionibacterium Acnes-induced Abnormal Proliferation and Keratinization of HaCat Cells by Regulating the S100A8/S100A9- MAPK Cascade.

BACKGROUND: Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown. METHODS: In the present study, acne was induced in the ears of rats using Propionibacterium acnes combined with sebum application. RESULTS: After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models. CONCLUSION: In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.

Functional outcomes and complications of patients contaminated with Cutibacterium acnes during primary reverse shoulder arthroplasty: study at two- and five-years of follow-up.

PURPOSE: The objective of the study was to compare the functional outcomes and the complication rate of the patients with C. acnes contamination at the end of the primary reverse shoulder arthroplasty (RSA) surgery to those patients without C. acnes contamination. METHOD: A total of 162 patients were included. In all cases, skin and deep tissue cultures were obtained. A molecular typing characterization of the C. acnes strains was performed. Functional outcomes were assessed with the Constant score at the two and five year follow-up and all complications were also recorded. RESULTS: A total of 1380 cultures were obtained from the 162 primary RSA surgeries. Of those, 96 turned out to be positive for C. acnes. There were 25 patients with positive cultures for C. acnes. The overall postoperative Constant score was not significantly different between those patients having C. acnes-positive cultures and those with negative cultures at the two and five year follow-up (59.2 vs. 59.6 at two years, p 0.870, and 59.5 vs. 62.4 at five years, p 0.360). Patients with positive cultures presented a higher complication rate (p 0.001) with two infections, one revision surgery, and one dislocation. CONCLUSION: Patients ending up with C. acnes-positive cultures after primary shoulder arthroplasty surgery do not have worse clinical outcomes when compared to patients having negative cultures, but a greater number of complications were found in those patients with C. acnes-positive cultures.

Active Ingredients of Schisandra chinensis Fruit Oil and their Effect on Propionibacterium acnes-Induced Inflammation in HaCaT Cells.

BACKGROUND: Propionibacterium acnes causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1ß, and tumor necrosis factor-alpha, increased levels of reactive oxygen species (ROS) and inward flow of calcium ions. This causes increased levels of the antimicrobial peptide LL-37 and inflammation of the skin, leading to redness, swelling, itching and other symptoms. Schisandra chinensis fruit oil (SCO) is rich in lignan active ingredients with various antioxidant and anti-inflammatory properties. METHODS: In this study, SCO is obtained by supercritical CO2 fluid extraction. SCO's anti-inflammatory actions were investigated using P. acnes-induced inflammation HaCaT cells model. A method based on reversed-phase high-pressure liquid chromatography with a diode array detector was developed and validated for the simultaneous detection of five lignan components. Levels of inflammatory factors and LL-37 were measured by ELISA kit and western blot respectively. Ca2+ and ROS levels detected by flow cytometry. RESULTS: The experimental results show that the contents of schisanol A, schisanol B, schisanin A, schisanin B, and schisanin C were 33.89 ± 0.24, 14.89 ± 0.45, 8.92 ± 0.02, 29.14 ± 0.67, and 4.74 ± 0.09 mg/g, respectively. Studies have demonstrated that SCO can alleviate skin inflammation by inhibiting the COX-2/PGE2 and NF-κB signalling pathway. In addition, SCO can inhibit ROS production, significantly block inward Ca2+ flow, alleviate cell damage, and modulate the content of the antimicrobial peptide LL-37. CONCLUSIONS: In summary, our study elucidated the anti-inflammatory activity of SCO in a cell model and provided a scientific basis for its application as a raw material in skin care.