Intestinal Invasion Research Articles

Salmonella Biomimetic Nanoparticles for Photothermal-Chemotherapy of Colorectal Cancer.

Nanomedicines have been widely used in colorectal cancer treatment, but their suboptimal targeting and deficient penetration capabilities remain obstacles in the delivery of therapeutics. In this study, inspired by the natural tumor tropism and intestinal invasion of Salmonella, we engineered highly biomimetic nanoparticles (SM-AuNRs) utilizing a Salmonella membrane to coat bacilliform Au nanorods. The engineered SM-AuNRs were able to mimic the germ's morphology and biological surface. SM-AuNRs containing the specific proteins inherited from the Salmonella membrane facilitated specific targeting and internalization into tumor cells. Meanwhile, SM-AuNRs with the rod-shaped morphology effectively traversed mucus barriers and tumor stroma. Due to the superior biological barrier penetrating and tumor targeting capabilities, doxorubicin-loaded SM-AuNRs with near-infrared laser irradiation displayed remarkable photothermal-chemotherapeutic antitumor effects in mouse orthotopic colorectal cancer models. Our findings pave the way for the design of bacteria-mimicking nanoparticles, presenting a promising avenue for the targeting and efficient treatment of colorectal cancer.

Astragalus polysaccharides-induced gut microbiota play a predominant role in enhancing of intestinal barrier function of broiler chickens

BackgroundThe intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota. Astragalus polysaccharides (APS) have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function. The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed.ResultsDietary polysaccharide deprivation induced intestinal barrier dysfunction, decreased growth performance, altered microbial composition (Faecalibacterium, Dorea, and Coprobacillus), and reduced isobutyrate concentration. The results showed that APS facilitates intestinal barrier function in broiler chickens, including a thicker mucus layer, reduced crypt depth, and the growth of tight junction proteins. We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides, a commensal bacterium that plays a predominant role in enhancing intestinal barrier function. An in vitro growth assay further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis. Dietary APS supplementation increased the concentrations of isobutyrate and bile acid (mainly chenodeoxycholic acid and deoxycholate acid) and activated signaling pathways related to intestinal barrier function (such as protein processing in the endoplasmic reticulum, tight junctions, and adherens junction signaling pathways).ConclusionsAPS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis, and increasing the concentrations of isobutyrate and bile acids (mainly CDCA and DCA). These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.Graphical

Venous thromboembolism in patients with pancreatic adenocarcinoma: Disease burden and initiation of ambulatory thromboprophylaxis

Background/ObjectivesAmbulatory thromboprophylaxis (AT) in patients with pancreatic adenocarcinoma (PAC) reduces venous thromboembolism (VTE) risk and is recommended for patients receiving systemic chemotherapy. We evaluated VTE rates, severity, timing, and risk factors in PAC patients as well as AT rates and initiation times. MethodsPatients diagnosed with PAC were included. Data collected included patient demographics, medical history, PAC diagnosis, development of VTE, AT, and bleeding episodes. VTE was defined as a DVT or a PE. Patients were classified as receiving AT for VTE prevention if they received a prescription for outpatient anticoagulation. ResultsThe cohort included 243 PAC patients. VTE occurred in 24 %. Overall, 52 % developing VTE were hospitalized and 5 % died as a result of the VTE. Of those who developed VTE 50 % were diagnosed within the first 2 months of PAC diagnosis. Univariate predictors of elevated VTE risk included an elevated Onkotev score, metastasis at diagnosis, male gender and not receiving AT. Multivariate predictors of elevated VTE risk included male gender (P = 0.014) and not receiving AT (P = 0.001). Overall, 30 % of patients received AT. The median time from diagnosis to initiation of AT was 43 days. Major bleeding occurred in 5.8 %. Patients receiving AT were not at a significantly increased risk of major bleeding (p = 0.5). Patients with intestinal tumor invasion were at significantly increased risk of major bleeding (P = 0.021). ConclusionVTE risk is significant and morbid in PAC patients. AT rates are low, and initiation is often delayed. Therapeutic endoscopists diagnosing PAC may be helpful in AT initiation.

Correlation between MR semiotics and intensity of pelvic pain syndrome in female patients with deep infiltrating endometriosis of the posterior pelvic compartment

Objective. To identify the correlation between magnetic resonance (MR) semiotics and the intensity of pelvic pain syndrome in female patients with deep infiltrating endometriosis of the posterior pelvic compartment. Material and methods. We performed a retro- and prospective analysis of MR studies of pelvic organs in 77 female patients with pelvic pain syndrome, aged from 24 to 39 years. We assessed the intensity of the pain syndrome using a visual analog scale (VAS). The patients were divided into 2 groups: 1st-patients with external genital endometriosis (EGE) without involving the posterior pelvic compartment, 2nd-patients with EGE of the posterior pelvic compartment. The patients of the second group were divided into subgroups: 1 – endometriosis of the posterior pelvic compartment without MR signs of intestinal wall invasion, 2 – posterior compartment endometriosis with MR signs of intestinal wall invasion. The study was conducted on a GE Signa 1.5 Tesla MRI scanner. Results. In the second group of patients with endometriosis of the posterior pelvic compartment, the pain syndrome (8.00 (7.00–9.00) was more intense than in the first group of patients without endometriosis of the posterior pelvic compartment 7.00 (5.00–7.00), p<0.001 and we evaluated a retrovaginal, retrocervical and posterior uterine localization. In the second subgroup of patients with signs of the intestinal wall invasion, the pelvic pain syndrome on the VAS was statistically significantly more intense 8.00 (8.00-10.00) than in the first subgroup of patients without signs of the intestinal wall invasion 7.00 (6.00–7.00) (P<0.001). Conclusion. Patients with identified deep infiltrating endometriosis of the posterior pelvic compartment have more pronounced manifestations of the pelvic pain syndrome then patients with endometriosis of other localizations.

The Incidence of Necrotizing Enterocolitis and Late-Onset Sepsis during the COVID-19 Pandemic in Sweden: A Population-Based Cohort Study

Introduction: The effect of the pandemic restrictions in the NICUs is not well studied. Necrotizing enterocolitis (NEC) is characterized by intestinal inflammation and bacterial invasion. This study aimed to investigate whether the incidence of NEC has changed during the COVID-19 pandemic in Sweden and whether it was associated with a change in the frequency of extremely preterm births. Methods: Data were retrieved from the Swedish Neonatal Quality Register (SNQ) for infants registered between January 2017 and December 2021 born below a gestational age of 35 weeks. The registry completeness is 98–99%. The diagnosis of NEC was the primary outcome. Generalized linear model analysis was used to calculate the risk ratio for NEC. Results: Totally 13,239 infants were included. 235 (1.8%) infants developed NEC, out of which 91 required surgical treatment. 8,967 infants were born before COVID-19 pandemic and 4,272 during. Median gestational age at birth was 32.8 weeks in both periods. The incidence of NEC was significantly lower during COVID-19 pandemic compared to the prior period (1.43 vs. 1.94%, p 0.037), but not the incidence of surgical NEC. The crude risk ratio of developing NEC during COVID-19 pandemic was 0.74 (95% CI: 0.55–0.98). The incidence of late-onset sepsis with positive culture was also declined during COVID-19 (3.21 vs. 4.15%, p value 0.008). Conclusion: While we found significant reduction in the incidence of NEC and culture-positive late-onset sepsis during the COVID-19 pandemic, the number of extremely preterm births was unchanged.

Major primary bile salts repress Salmonella enterica serovar Typhimurium invasiveness partly via the efflux regulatory locus ramRA.

Bile represses Salmonella enterica serovar Typhimurium (S. Typhimurium) intestinal cell invasion, but it remains unclear which bile components and mechanisms are implicated. Previous studies reported that bile inhibits the RamR binding to the ramA promoter, resulting in ramA increased transcription, and that ramA overexpression is associated to decreased expression of type III secretion system 1 (TTSS-1) invasion genes and to impaired intestinal cell invasiveness in S. Typhimurium. In this study, we assessed the possible involvement of the ramRA multidrug efflux regulatory locus and individual bile salts in the bile-mediated repression of S. Typhimurium invasion, using Caco-2 intestinal epithelial cells and S. Typhimurium strain ATCC 14028s. Our results indicate that (i) major primary bile salts, chenodeoxycholate and its conjugated-derivative salts, cholate, and deoxycholate, activate ramA transcription in a RamR-dependent manner, and (ii) it results in repression of hilA, encoding the master activator of TTSS-1 genes, and as a consequence in the repression of cellular invasiveness. On the other hand, crude ox bile extract and cholate were also shown to repress the transcription of hilA independently of RamR, and to inhibit cell invasion independently of ramRA. Altogether, these data suggest that bile-mediated repression of S. Typhimurium invasion occurs through pleiotropic effects involving partly ramRA, as well as other unknown regulatory pathways. Bile components other than the bile salts used in this study might also participate in this phenomenon.

Risk factors of necrotizing enterocolitis among neonates admitted to the neonatal intensive care unit at the selected public hospitals in southern Ethiopia, 2023.

Necrotizing enterocolitis (NEC) is a serious intestinal condition characterized by ischemic necrosis of the intestinal mucosa, inflammation, and invasion by gas-forming organisms, posing a significant threat to neonatal health. Necrotizing enterocolitis remains a significant cause of neonatal morbidity and mortality, particularly in developing countries. Due to limited research conducted in Ethiopia and the study area, there is a lack of information regarding the risk factors associated with necrotizing enterocolitis. Therefore, the goal of this study is to fill the aforementioned gap. This study aims to identify the risk factors of necrotizing enterocolitis among neonates admitted to the neonatal intensive care unit (NICU) at selected general and referral hospitals in southern Ethiopia in the year 2023. A facility-based unmatched case-control study was conducted. All neonates admitted to the NICU and diagnosed with necrotizing enterocolitis by the attending physician during the data collection period were considered as cases, whereas neonates admitted to the NICU but not diagnosed with necrotizing enterocolitis during the data collection period were considered as controls. Data were collected through face-to-face interviews and record reviews using the Kobo toolbox platform. The binary logistic regression method was used to determine the relationship between a dependent variable and independent variables. Finally, a p-value of < 0.05 was considered statistically significant. This study included 111 cases and 332 controls. Normal BMI [AOR = 0.11, 95% CI: (0.02, 0.58)], history of khat chewing [AOR = 4.21, 95% CI: (1.96, 9.06)], term gestation [AOR = 0.06, 95% CI: (0.01, 0.18)], history of cigarette smoking [AOR = 2.86, 95% CI: (1.14, 7.14)], length of hospital stay [AOR = 3.3, 95% CI: (1.43, 7.67)], and premature rupture of membrane [AOR = 3.51, 95% CI: (1.77, 6.98)] were significantly associated with NEC. The study identified several risk factors for necrotizing enterocolitis, including body mass index, history of khat chewing, gestational age, history of cigarette smoking, length of hospital stays, and premature rupture of membrane. Therefore, healthcare providers should be aware of these risk factors to identify newborns at high risk and implement preventive measures.

The Prophylactic Protection of Salmonella Typhimurium Infection by Lentilactobacillus buchneri GX0328-6 in Mice.

Salmonellosis is a disease caused by non-typhoid Salmonella, and although some lactic acid bacteria strains have been shown previously to relieve Salmonellosis symptoms, little has been studied about the preventive mechanism of Lentilactobacillus buchneri (L. buchneri) against Salmonella infection in vivo. Therefore, the L. buchneri was fed to C57BL/6 mice for 10days to build a protective system of mice to study its prevention and possible mechanisms. The results showed that L. buchneri GX0328-6 alleviated symptoms caused by Salmonella typhimurium infection among C57BL/6 mice, including low survival rate, weight loss, increase in immune organ index and hepatosplenomegaly, and modulated serum immunoglobulin levels and intrinsic immunity. Importantly, the L. buchneri GX0328-6 enhanced the mucosal barrier of the mouse jejunum by upregulating the expression of tight junction proteins such as ZO-1, occludins, and claudins-4 and improved absorptive capacity by increasing the length of mouse jejunal villus and the ratio of villus length to crypt depth and decreasing the crypt depth. L. buchneri GX0328-6 reduced the intestinal proliferation and invasion of Salmonella typhimurium by modulating the expression of antimicrobial peptides in the intestinal tract of mice, and reduced intestinal inflammation and systemic spread in mice by downregulating the expression of IL-6 and promoting the expression of IL-10. Furthermore, L. buchneri GX0328-6 increased the relative abundance of beneficial bacteria colonies and decreased the relative abundance of harmful bacteria in the cecum microflora by modulating the microflora in the cecum contents.

Unusual Behavior of Intestinal Spirochetosis: A Case Report

Abstract Human intestinal spirochetosis is a rare clinicopathological condition characterized by the presence of spirochetal microorganisms on the surface of the colorectal mucosa and, in some cases, by their invasion into the lamina propria. The most frequent cause of this infection is immunocompromised status. Our case report describes a patient with relevant symptoms and endoscopic alterations, but limited invasion by spirochetes, as shown by histological analysis of ileal and colonic specimens. After histological examination, metronidazole was initiated. This resulted in rapid and complete resolution of the symptoms, which demonstrated an infectious etiology. The peculiarity of our case is that the clinical and endoscopic appearances were typical of the aggressive behavior of the disease, but histological samples showed only superficial colonization of the colonic epithelium without clear invasion of deeper layers. This case report emphasizes that the virulence of spirochetes is not strictly related to intestinal mucosal invasion.

A clinical case of small intestinal intussusception caused by metastatic melanoma

Intestinal obstruction is observed in about 9.0 % of patients with acute surgical pathology of the abdominal cavity. The disease occurs at any age, but more often between 25–50 years. Mixed intestinal obstruction is only 3–7 %. The most common form of mixed intestinal obstruction is intestinal invasion. The most common cause of intussusception in adults is an intestinal tumor. Early diagnosis and the optimal amount of surgical treatment are the main components of successful treatment of the patient.&#x0D; Aim: to familiarize practitioners with a rare case of intestinal obstruction in adults and its management strategies in a surgical hospital.&#x0D; Materials and methods. The patient was treated in the surgical department of the Communal Non-Profit Enterprise “City Hospital No. 7” Zaporizhzhia City Consul. The patient underwent preoperative preparation and surgical intervention.&#x0D; Results. The patient underwent an emergency median laparotomy under total intravenous anesthesia with artificial lung ventilation. During the examination of the abdominal cavity, multiple distended loops of the small intestine were visualized. During the revision, at a distance of 1.5 meters from the ligament of Treitz, a volumetric formation of the small intestine of dense-elastic consistency, represented by small-intestinal invasion, up to 10 cm long, was detected. The proximal sections of the small intestine are distended, light purple in color. The sections of the small intestine that were distal to the site of invasion were inflamed. Manual disinvagination of the small intestine was performed. The visual examination showed that the intestine was viable. There was a tumor was found on the antrumeral margin, measuring 1.8 × 2.5 cm, dense in consistency, finely tuberculated, dark purple heterogeneous in color, infiltrating and deforming the wall of the small intestine. Resection of the invaded area of the small intestine with the tumor was performed with the imposition of a small-small intestinal anastomosis “side to side” with two-row nylon sutures.&#x0D; Conclusions. In this clinical case, it was possible to establish the final diagnosis and determine further surgical strategy only intraoperatively. Only early diagnosis of melanoma will allow avoiding the complications identified in this patient.

In vitro knockdown of TsDNase II-7 suppresses Trichinella spiralis invasion into the host's intestinal epithelial cells.

Trichinella spiralis (T. spiralis) adult-specific deoxyribonuclease II-7 (TsDNase II-7), a member of the DNase II-like nuclease family with no DNase II activity, was identified in the excretory-secretory (ES) products of adult worms (AWs). However, its biological functions are still unclear. Our previous study revealed that TsDNase II-7 is located around the infection site in the intestinal tissue, speculating that it was involved in the T. spiralis invasion of host intestinal epithelial cells (IECs). This study aimed to use RNA interference to verify our speculation that TsDNase II-7 in 3-day old adult T. spiralis (Ad3) plays a role in intestinal invasion. TsDNase II-7-specific small interfering RNAs (siRNAs) were delivered into muscle larvae (MLs) to knockdown TsDNase II-7 expression by electroporation. Twenty-four hours later, the MLs transfected with 2 μM siRNA-841 exhibited decreased in TsDNase II-7 transcription and expression as compared to the control MLs. The knockdown of TsDNase II-7 expression did not affect ML viability, and the low expression of TsDNase II-7 still maintained in Ad3 recovered from TsDNase II-7-RNAi-ML infected mice, resulting in a weakened ability of Ad3 to invade intestinal epithelial cells (IECs). These results indicated that knockdown of TsDNase II-7 gene expression via RNA interference (RNAi) suppressed adult worm invasion and confirmed that TsDNase II-7 plays a crucial role during the intestinal phase of T. spiralis infections, which provided new candidate for vaccine development of T. spiralis.

Gene expression and cell culture assays reveal cheese isolate Lactococcus lactis MC5 may influence the virulence of Staphylococcus aureus.

Staphylococcus aureus (SA) can thrive in a wide variety of hosts and environments, causing clinical infections and foodborne intoxications. In Brazil, SA is commonly isolated from traditional soft cheeses, especially those prepared from unpasteurized milk. In this research, the isolate S. aureus SABRC1 was evaluated for virulence traits under different conditions, including co-inoculation with Lactococcus lactis MC5 (isolated from "Fresh Minas Cheese"), which produces antibacterial peptides. Results from experiments with Caco-2 culture indicated S. aureus SABRC1 was able to adhere (42.83 ± 1.79%) and to invade (48.57 ± 0.41%) the intestinal cells. On the other hand, L. lactis MC5 presented anti-staphylococcal activity as indicated by agar assays, and it was also able to antagonize intestinal cell invasion by S. aureus. Moreover, Reverse Transcriptase-PCR experiments showed virulence genes of S. aureus SABRC1 (hla, icaA and sea) were differentially expressed under diverse culture conditions, which included Brain Heart Infusion modified or not by the addition of glucose, sodium chloride, milk or cheese. This suggests the virulence of S. aureus SABRC1 is influenced by compounds commonly found in daily diets, and not only by its genetic repertoire, adding a novel level of complexity for controlling infection by this pathogen.

Intestinal Candida albicans overgrowth in IgA deficiency

Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, it remains unknown whether human IgA-deficiency is associated with gut fungal dysbiosis. Our goal was to study the impact of IgA on gut mycobiota ecology. The Fungi-flow method was used to characterize fecal, systemic, and maternal IgA, IgM and IgG responses against 14 representative fungal strains (yeast/spores or hyphae forms) in healthy donors (HD, n= 34, 31 and 20, respectively), and also to compare gut mycobiota opsonization by secretory antibodies in HD (n=28) and patients with selective IgA deficiency (SIgAd n=12). Stool mycobiota composition was determined by ITS gene sequencing in HD (n= 23) and SIgAd (n=17). Circulating CD4+ T cell cytokine secretion profiles were determined by intracellular staining. Impact of secretory IgA, purified from breast milk (n=9), on candida growth and intestinal Caco-2 cell invasion was tested in vitro. Homeostatic IgA binds commensal fungi with a body fluid-selective pattern of recognition. In SIgAd patients, fungal gut ecology is preserved by compensatory IgM binding to commensal fungi. Gut Candida albicans overgrowth nevertheless occurs in this condition, but only in clinically symptomatic patients with decreased Th17/22 T cell responses. Indeed, secretory IgA can reduce in vitro budding and invasion of intestinal cells by C. albicans, and therefore exert control on this pathobiont. IgA has a selective impact on C. albicans ecology to preserve fungal-host mutualism.

SaaS sRNA promotes Salmonella intestinal invasion via modulating MAPK inflammatory pathway

ABSTRACT Salmonella Enteritidis is a foodborne enteric pathogen that infects humans and animals, utilizing complex survival strategies. Bacterial small RNA (sRNA) plays an important role in these strategies. However, the virulence regulatory network of S. Enteritidis remains largely incomplete and knowledge of gut virulence mechanisms of sRNAs is limited. Here, we characterized the function of a previously identified S almonella adhesive-associated sRNA (SaaS) in the intestinal pathogenesis of S. Enteritidis. We found that SaaS promoted bacterial colonization in both cecum and colon of a BALB/c mouse model; it was preferentially expressed in colon. Moreover, our results showed that SaaS enhanced damage to mucosal barrier by affecting expressions of antimicrobial products, decreasing the number of goblet cells, suppressing mucin gene expression, and eventually reducing thickness of mucus layer; it further breached below physical barrier by strengthening invasion into epithelial cells in Caco-2 cell model as well as decreasing tight junction expressions. High throughput 16S rRNA gene sequencing revealed that SaaS also altered gut homeostasis by depleting beneficial gut microbiota while increasing harmful ones. Furthermore, by employing ELISA and western blot analysis, we demonstrated that SaaS regulated intestinal inflammation through sequential activation P38-JNK-ERK MAPK signaling pathway, which enabled immune escape at primary infection stage but strengthened pathogenesis at later stage, respectively. These findings suggest that SaaS plays an essential role in the virulence of S. Enteritidis and reveals its biological role in intestinal pathogenesis.

Gut microbiota-derived 3-phenylpropionic acid promotes intestinal epithelial barrier function via AhR signaling

BackgroundThe intestinal epithelial barrier confers protection against the intestinal invasion by pathogens and exposure to food antigens and toxins. Growing studies have linked the gut microbiota to the intestinal epithelial barrier function. The mining of the gut microbes that facilitate the function of intestinal epithelial barrier is urgently needed.ResultsHere, we studied a landscape of the gut microbiome of seven pig breeds using metagenomics and 16S rDNA gene amplicon sequencing. The results indicated an obvious difference in the gut microbiome between Congjiang miniature (CM) pigs (a native Chinese breed) and commercial Duroc × [Landrace × Yorkshire] (DLY) pigs. CM finishing pigs had stronger intestinal epithelial barrier function than the DLY finishing pigs. Fecal microbiota transplantation from CM and DLY finishing pigs to germ-free (GF) mice transferred the intestinal epithelial barrier characteristics. By comparing the gut microbiome of the recipient GF mice, we identified and validated Bacteroides fragilis as a microbial species that contributes to the intestinal epithelial barrier. B. fragilis-derived 3-phenylpropionic acid metabolite had an important function on the enhancement of intestinal epithelial barrier. Furthermore, 3-phenylpropionic acid facilitated the intestinal epithelial barrier by activating aryl hydrocarbon receptor (AhR) signaling.ConclusionsThese findings suggest that manipulation of B. fragilis and 3-phenylpropionic acid is a promising strategy for improving intestinal epithelial barrier.2w7rc9SeP7MH5hV22czHPoVideo

Inflammatory monocytes promote granuloma control of Yersinia infection.

Granulomas are organized immune cell aggregates formed in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis (Yp) blocks innate inflammatory signalling and immune defence, inducing neutrophil-rich pyogranulomas (PGs) within lymphoid tissues. Here we uncover that Yp also triggers PG formation within the murine intestinal mucosa. Mice lacking circulating monocytes fail to form defined PGs, have defects in neutrophil activation and succumb to Yp infection. Yersinia lacking virulence factors that target actin polymerization to block phagocytosis and reactive oxygen burst do not induce PGs, indicating that intestinal PGs form in response to Yp disruption of cytoskeletal dynamics. Notably, mutation of the virulence factor YopH restores PG formation and control of Yp in mice lacking circulating monocytes, demonstrating that monocytes override YopH-dependent blockade of innate immune defence. This work reveals an unappreciated site of Yersinia intestinal invasion and defines host and pathogen drivers of intestinal granuloma formation.

Severe acute respiratory syndrome coronavirus-2 Alpha variant (B.1.1.7), original wild-type severe acute respiratory syndrome coronavirus 2, and cytomegalovirus co-infection in a young adult with acute lymphoblastic leukemia, case report, and review of the possible cytomegalovirus reactivation mechanisms

BackgroundLike other viral infections, severe acute respiratory syndrome coronavirus-2 infection could affect different human body systems, including host immune responses. Three years after its pandemic, we learn more about this novel coronavirus. As we expected, different co-infections with various organisms, such as viruses, bacteria, and even fungi, have been reported. However, concurrent infection with two severe acute respiratory syndrome coronavirus-2 strains and cytomegalovirus is extremely unusual. We have only a rudimentary understanding of such co-infections and their long-term consequences for patients with cancer.Case presentationAn 18-year-old young Iranian adult with acute lymphoblastic leukemia presented with abdominal pain, diarrhea, nausea, and vomiting following a recent history of severe acute respiratory syndrome coronavirus-2 infection. The patient never experienced respiratory symptoms, and the chest imaging study was normal on admission. His primary laboratory investigation revealed prerenal azotemia and severe abnormal liver function tests (blood urea nitrogen 32 mg/dL, creatinine 1.75 mg/dL, prothrombin time 66 s, partial thromboplastin time 44.5 s, international normalized ratio 5.14, total bilirubin 2.9 mg/dL, and direct bilirubin 2.59 mg/dL). Cytomegalovirus disease was diagnosed by polymerase chain reaction in his blood and stool samples. The patient’s gastrointestinal signs and symptoms improved shortly after receiving intravenous ganciclovir treatment. His gastrointestinal symptoms continued intermittently for weeks despite maintenance valganciclovir prescription, necessitating frequent hospitalizations. The patient was complicated by the recurrence of gastrointestinal symptoms during the sixth hospitalization, even though he had no respiratory symptoms, and the nasopharyngeal test revealed severe acute respiratory syndrome coronavirus-2 Wuhan strain for the first time. Remdesivir and valganciclovir were administrated due to persistent enteritis and evidence of intestinal tissue invasion by severe acute respiratory syndrome coronavirus 2 and cytomegalovirus on multiple intestinal biopsies, which led to partial clinical responses. Cytomegalovirus and severe acute respiratory syndrome coronavirus-2 fecal shedding continued for more than 6 months despite repeated antiviral therapy, and the Wuhan and Alpha strains were also detected in his nasopharyngeal samples through repeated sampling (confirmed by four nasopharyngeal sampling and multiple stool specimens and several intestinal biopsies). Finally, during the Delta-variant (B.1.617.2) outbreak in Iran, the patient was admitted again with febrile neutropenia and decreased level of consciousness, necessitating respiratory support and mechanical ventilation. During the Delta-variant peak, the patient’s nasopharyngeal sample once more tested positive for severe acute respiratory syndrome coronavirus 2. The patient died a few days later from cardiopulmonary arrest.ConclusionThe coronavirus disease 2019 pandemic has encountered patients with cancer with critical diagnostic and treatment challenges. Patients who are immunocompromised may co-infect with multiple severe acute respiratory syndrome coronavirus-2 strains and cytomegalovirus, and even with timely diagnosis and treatment, the prognosis may be poor.

Diagnostic value of endoscopic ultrasonography in pelvic masses with bowel involvement.

Benign and malignant pelvic masses with or without intestinal invasion are common in women of childbearing age. Patients may have nonspecific symptoms and signs or experience no symptoms. Laparoscopic resection of pelvic masses is currently the mainstream treatment; therefore, accurate preoperative evaluation is not only essential for patients suspected of having intestinal invasion, but also extremely important for the selection of follow-up treatment. Procedures, including endoscopic ultrasonography (EUS), pelvic magnetic resonance imaging, abdominal computed tomography, vaginal ultrasonography, barium enema, and colonoscopy, aid in determining the presence, depth, and histology of the disease. In particular, the wide application and continuous developments in EUS techniques have improved the diagnostic accuracy for intestinal subepithelial and peripheral organ lesions. This article reviewed the clinical value of EUS in the diagnosis of benign and malignant pelvic masses with bowel involvement.

Effects of intestinal microbiota on physiological metabolism and pathogenicity of Vibrio.

Vibrio species are disseminated broadly in the marine environment. Some of them can cause severe gastroenteritis by contaminating seafood and drinking water, such as Vibrio parahaemolyticus, Vibrio cholerae, and Vibrio vulnificus. However, their pathogenic mechanism still needs to be revealed to prevent and reduce morbidity. This review comprehensively introduces and discusses the common pathogenic process of Vibrio including adhesion, cell colonization and proliferation, and resistance to host immunity. Vibrio usually produces pathogenic factors including hemolysin, type-III secretion system, and adhesion proteins. Quorum sensing, a cell molecular communication system between the bacterial cells, plays an important role in Vibrio intestinal invasion and colonization. The human immune system can limit the virulence of Vibrio or even kill the bacteria through different responses. The intestinal microbiota is a key component of the immune system, but information on its effects on physiological metabolism and pathogenicity of Vibrio is seldom available. In this review, the effects of intestinal microorganisms and their metabolites on the invasion and colonization of common pathogenic Vibrio and VBNC status cells are discussed, which is conducive to finding the next-generation prebiotics. The strategy of dietary intervention is discussed for food safety control. Finally, future perspectives are proposed to prevent Vibrio infection in aquaculture.

Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. The putative chitinase STM0233 has not been studied previously, and only limited data exists on ChiA. Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome.