Salmonella is the leading cause of food-borne zoonotic disease worldwide. Non-typhoidal Salmonella serotypes are the primary etiological agents associated with salmonellosis in poultry. Contaminated poultry eggs and meat products are the major sources of human Salmonella infection. Horizontal and vertical transmission are the primary routes of infection in chickens. The principal virulence genes linked to Salmonella pathogenesis in poultry are located in Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2). Cell-mediated and humoral immune responses are involved in the defense against Salmonella invasion in poultry. Vaccination of chickens and supplementation of feed additives like prebiotics, probiotics, postbiotics, synbiotics, and bacteriophages are currently being used to mitigate the Salmonella load in poultry. Despite the existence of various control measures, there is still a need for a broad, safe, and well-defined strategy that can confer long-term protection from Salmonella in poultry flocks. This review examines the current knowledge on the etiology, transmission, cell wall structure, nomenclature, pathogenesis, immune response, and efficacy of preventative approaches to Salmonella.

Salmonella Infection in Poultry: A Review on the Pathogen and Control Strategies

Polygonati Rhizoma is a widely used traditional Chinese medicine (TCM) with complex pre-processing steps. Fermentation is a common method for processing TCM to reduce herb toxicity and enhance their properties and/or produce new effects. Here, in this study, using Bacillus subtilis and Saccharomyces cerevisiae, we aimed to evaluate the potential application of solid fermentation in isolating different functional polysaccharides from Polygonatum cyrtonema Hua. With hot water extraction, ethanol precipitation, DEAE anion exchange chromatography and gel filtration, multiple neutral and acidic polysaccharides were obtained, showing different yields, content, compositions and functional groups after fermentation. Combining in vitro experiments and in vivo aging and immunosuppressed mouse models, we further compared the antioxidant and immunomodulating bioactivities of these polysaccharides and found a prominent role of a natural polysaccharide (BNP) from fermented P. cyrtonema via Bacillus subtilis in regulating intestinal antioxidant defense and immune function, which may be a consequence of the ability of BNP to modulate the homeostasis of gut microbiota. Thus, this work provides evidence for the further development and utilization of P. cyrtonema with fermentation, and reveals the potential values of BNP in the treatment of intestinal disorders.

Effects of Solid Fermentation on Polygonatum cyrtonema Polysaccharides: Isolation, Characterization and Bioactivities

Contrast-enhanced ultrasound (CEUS) is a dependable modality for the diagnosis of various clinical conditions. A judicious selection of ultrasound contrast agent (UCA) is imperative for optimizing imaging and improving diagnosis. Approved UCAs for imaging the majority of organs include SonoVue, a pure blood agent, and Sonazoid, which exhibits an additional Kupffer phase. Despite the fact that the two UCAs are increasingly being employed, there is a lack of comparative reviews between the two agents in different organs diseases. This review represents the first attempt to compare the two UCAs in non-hepatic organs, primarily including breast, thyroid, pancreas, and spleen diseases. Through comparative analysis, this review provides a comprehensive and objective evaluation of the performance characteristics of SonoVue and Sonazoid, with the aim of offering valuable guidance for the clinical application of CEUS. Overall, further clinical evidences are required to compare and contrast the dissimilarities between the two UCAs in non-hepatic organs, enabling clinicians to make an appropriate selection based on actual clinical applications. 

A review of contrast-enhanced ultrasound using SonoVue® and Sonazoid™ in non-hepatic organs.

Colonisation by bacterial pathogens typically precedes invasive infection and seeds transmission. Thus, effective decolonisation strategies are urgently needed. The literature reports attempts to use phages for decolonisation. To assess the in-vivo efficacy and safety of phages for bacterial decolonisation, we performed a systematic review by identifying relevant studies to assess the in-vivo efficacy and safety of phages for bacterial decolonisation. We searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and the Cochrane Library to identify relevant articles published between Jan 1, 1990, and May 12, 2023, without language restrictions. We included studies that assessed the efficacy of phage for bacterial decolonisation in humans or vertebrate animal models. This systematic review is registered with PROSPERO, CRD42023457637. We identified 6694 articles, of which 56 (51 animal studies and five clinical reports) met the predetermined selection criteria and were included in the final analysis. The gastrointestinal tract (n=49, 88%) was the most studied bacterial colonisation site, and other sites were central venous catheters, lung, nose, skin, and urinary tract. Of the 56 included studies, the bacterial load at the colonisation site was reported to decrease significantly in 45 (80%) studies, but only five described eradication of the target bacteria. 15 studies reported the safety of phages for decolonisation. No obvious adverse events were reported in both the short-term and long-term observation period. Given the increasing life-threatening risks posed by bacteria that are difficult to treat, phages could be an alternative option for bacterial decolonisation, although further optimisation is required before their application to meet clinical needs. 

Safety and efficacy of phage application in bacterial decolonisation: a systematic review.

Abstract The lasso peptide microcin Y (MccY) effectively inhibits various serotypes of Salmonella in vitro, but the antibacterial effect against S . Pullorum in poultry is still unclear. This study was the first to evaluate the safety and anti- S . Pullorum infection of MccY in specific pathogen-free (SPF) chicks. The safety test showed that the body weight, IgA and IgM levels of serum, and cecal microbiota structure of 3 groups of chicks orally administrated with different doses of MccY (5 mg/kg, 10 mg/kg, 20 mg/kg) for 14 days were not significantly different from those of the control group. Then, the chicks were randomized into 3 groups for the experiment of anti- S . Pullorum infection: (I) negative control group (NC), (II) S . Pullorum-challenged group (SP, 5 × 10 8 CFU/bird), (III) MccY-treated group (MccY, 20 mg/kg). The results indicated that compared to the SP group, treatment of MccY increased body weight and average daily gain ( P &lt; 0.05), reduced S . Pullorum burden in feces, liver, and cecum ( P &lt; 0.05), enhanced the thymus, and decreased the spleen and liver index ( P &lt; 0.05). Additionally, MccY increased the jejunal villus height, lowered the jejunal and ileal crypt depth ( P &lt; 0.05), and upregulated the expression of IL-4 , IL-10 , ZO-1 in the jejunum and ileum, as well as CLDN-1 in the jejunum ( P &lt; 0.05) compared to the SP group. Furthermore, MccY increased probiotic flora ( Barnesiella , etc.), while decreasing ( P &lt; 0.05) the relative abundance of pathogenic flora ( Escherichia and Salmonella , etc.) compared to the SP group. 

Effect of oral administration of microcin Y on growth performance, intestinal barrier function and gut microbiota of chicks challenged with Salmonella Pullorum

https://doi.org/10.1016/j.psj.2023.102715

Research Note: Therapeutic effect of a Salmonella phage combination on chicks infected with Salmonella Typhimurium

BACKGROUND
For patients with cN0 and T1-2 breast cancer, sentinel lymph node biopsy (SLNB) can provide survival results equivalent to axillary lymph node dissection (ALND). However, whether it can be performed on T3-4c patients is still controversial.


MATERIALS AND METHODS
Female patients diagnosed with cN0, T3-4c, and M0 breast cancer from 2004 to 2019 were identified using the surveillance, epidemiology and end results (SEER) database and divided into 2 groups, the SLNB group (1-5 regional lymph nodes examined) and the ALND group (≥10 regional lymph nodes examined). Finally, only those with pN0 disease were included in the SLNB group. The baseline differences in clinicopathological characteristics between groups were eliminated by propensity score matching (PSM). We also conducted subgroup analyses according to age, overall TNM stage, breast cancer subtypes, surgical approaches, radiation therapy, and chemotherapy. The primary endpoint was survival.


RESULTS
With a mean follow-up of 75 months, a total of 186 deaths were reported among 864 patients. The overall survival (OS) and breast cancer-specific survival (BCSS) in the SLNB group were 78.2% and 87.5%, respectively, and that in the ALND group were 78.7% and 87.3%, respectively. The unadjusted hazard ratio (HR) for OS and BCSS in the SLNB group (vs. the ALND group) was 0.922 (95% CI, 0.691-1.230, P = .580) and 0.874 (95% CI, 0.600-1.273, P = .481), respectively. Besides, the OS and BCSS between the 2 groups were also similar in all subgroup analyses.


CONCLUSIONS
SLNB may be performed on female patients with cN0, T3-4c, and M0 breast cancer.

Survival After Sentinel Lymph Node Biopsy Compared with Axillary Lymph Node Dissection for Female Patients with T3-4c Breast Cancer.

Salmonella enterica subsp. enterica serovar Gallinarum biovar pullorum (Salmonella pullorum) is an avian-specific pathogen that has caused considerable economic losses to the poultry industry. High endemicity, poor implementation of hygiene measures, and lack of effective vaccines hinder the prevention and control of this disease in intensively maintained poultry flocks. In recent years, the incidence of arthritis in chicks caused by Salmonella pullorum infection has increased. In this study, four Salmonella pullorum strains were identified from the livers, spleens, and joint fluids of Qingjiaoma chicken breeders with arthritis clinical signs, and an arthritis model of chicks was successfully established using SP206-2. Whole genome sequencing of the SP206-2 strain showed that the genome was 4,730,579 bp, 52.16% GC content, and contained 5007 genes, including 4729 protein-coding regions. The genomic analysis of four arthritis-causing isolates and three diarrhea-causing isolates showed that the genome of arthritis-causing isolates was subject to nonsynonymous mutations, shift mutations, and gene copy deletions. An SNP phylogenetic tree analysis showed that arthritis-causing isolates are located in a different evolutionary branch from diarrhea-causing isolates. Further differential genes analysis showed that the genome of arthritis-causing isolates had missense mutations in genes related to substance metabolism and substance transport, as a result of adaptive evolution.

The Genomic Characteristics of an Arthritis-Causing Salmonella pullorum

Simple Summary Salmonella enterica serovar Gallinarum biovar Pullorum (S. Pullorum), a septicemic pathogenic bacterium of poultry due to high mortality of chicks or poults, could not only result in a high mortality rate among embryos and chicks, but also lead to persistent infection and transmission to eggs or progeny in adult chickens during the carrier state. Diseases caused by Salmonella infection via vertical transmission continue to pose a highly significant threat to both human and animals; however, research on phage therapy regarding the vertical transmission of Salmonella is currently lacking. In this study, we evaluated the effect of Salmonella phage CKT1 on controlling the vertical infection of S. Pullorum by detecting the bacterial load in the reproductive system, eggshells and liquid whole eggs of adult broiler breeders. The results showed that the oral use of phage CKT1 could effectively reduce the colonization level of S. Pullorum in various organs including liver, spleen, heart, ovary and oviduct of adult breeders. More importantly, phage treatment significantly decreased the Salmonella-specific IgG level in serum of infected chickens, and reduced the bacterial load in eggshells and liquid whole eggs, thus decreasing the probability of vertical transmission of S. Pullorum in poultry. In addition, the total bacterial load in the poultry breeding environment was also significantly reduced after phage therapy, probably due to the decrease in the Salmonella load in cecal contents and restoration of the intestinal microbiome in chickens. Abstract Phage therapy is widely being reconsidered as an alternative to antibiotics for the treatment of multidrug-resistant bacterial infections, including salmonellosis caused by Salmonella. As facultative intracellular parasites, Salmonella could spread by vertical transmission and pose a great threat to both human and animal health; however, whether phage treatment might provide an optional strategy for controlling bacterial vertical infection remains unknown. Herein, we explored the effect of phage therapy on controlling the vertical transmission of Salmonella enterica serovar Gallinarum biovar Pullorum (S. Pullorum), a poultry pathogen that causes economic losses worldwide due to high mortality and morbidity. A Salmonella phage CKT1 with lysis ability against several S. enterica serovars was isolated and showed that it could inhibit the proliferation of S. Pullorum in vitro efficiently. We then evaluated the effect of phage CKT1 on controlling the vertical transmission of S. Pullorum in an adult broiler breeder model. The results demonstrated that phage CKT1 significantly alleviated hepatic injury and decreased bacterial load in the liver, spleen, heart, ovary, and oviduct of hens, implying that phage CKT1 played an active role in the elimination of Salmonella colonization in adult chickens. Additionally, phage CKT1 enabled a reduction in the Salmonella-specific IgG level in the serum of infected chickens. More importantly, the decrease in the S. Pullorum load on eggshells and in liquid whole eggs revealed that phage CKT1 effectively controlled the vertical transmission of S. Pullorum from hens to laid eggs, indicating the potential ability of phages to control bacterial vertical transmission.

/pdf/salmonella-phage-ckt1-effectively-controls-the-vertical-210ar6ti.pdf

Salmonella Phage CKT1 Effectively Controls the Vertical Transmission of Salmonella Pullorum in Adult Broiler Breeders

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Research Note: Therapeutic effect of a Salmonella phage combination on chicks infected with Salmonella Typhimurium

Survival After Sentinel Lymph Node Biopsy Compared with Axillary Lymph Node Dissection for Female Patients with T3-4c Breast Cancer.

The Genomic Characteristics of an Arthritis-Causing Salmonella pullorum

Salmonella Phage CKT1 Effectively Controls the Vertical Transmission of Salmonella Pullorum in Adult Broiler Breeders