Mesenchymal stem cell (MSC) based cell therapy has emerged as a promising therapeutic approach for treatment of several degenerative, infectious and non-infectious diseases. Numerous studies have demonstrated the remarkable immunosuppressive and antibacterial effects of MSCs both in vitro and in vivo, in animal models and in humans. However, the antibacterial effects of MSCs rely heavily on their paracrine factors rather than direct cell-to-cell contact and the effect is specific to disease and site of infection or injury. Furthermore, recent studies have demonstrated the double-edged sword effect of MSCs in bacterial infectious diseases. Despite their inherent potential for repair of damaged tissues, immunosuppression, and alleviation of various autoimmune as well as infectious diseases, MSCs also play a critical role in promoting persistent bacterial infection and disease progression. Therapeutic administration of MSCs successfully inhibited the bacterial growth and enhances survival by improved clearance of pathogenic bacteria in sepsis and pneumonic conditions. However, due to their abnormal transformation, they assist in long lasting survival and persistent infection of Mycobacterium tuberculosis (M. tuberculosis) and may also be responsible for progression of gastric cancer. This review focuses on recent advances that have broadened our understanding of MSC based therapy for bacterial diseases and provides new insight into the possible therapeutic targets of fatal bacterial diseases.
Inflammation mainly mediated by innate immune cells as the first line of host defense against pathogens is an acute response that limits tissue damage and eliminates pathogens in the body. In triggering inflammation, several pattern recognition receptors work together; membrane-associated Toll-like receptors, c-type lectin receptors, retinoic acid-inducible gene-like helicase receptors, absent in melanoma-like receptors, and cytosolic nucleotide-binding domain and leucine-rich repeat receptors. Among them, inflammasome is a newly trigger of inflammation in response to exogenous and endogenous stimuli and its activation leads to the assembly of multiprotein platforms composed of NLRP3 (NOD-like receptor family, pyrin domain containing 3), ASC (apoptosis associated speck-like protein containing a CARD), and procaspase 1. Thus, the activated inflammasome activates caspase 1, resulting in processing and secretion of interleukin (IL)-1β. Recent emerging data suggest that dysregulated metabolites, i.e., amyloids, ceramides, and cholesterol crystals, have been classified as inflammasome activators. In addition, IL-1β may play a critical role in the pathogenesis of chronic inflammation-induced disorders such as Alzheimer’s diseases, type 2 diabetes, and atheriosclerosis. This review introduces the basic concept of inflammasome activation and auto-inflammatory diseases. In addition, it discusses the updated signaling models of inflammasome activation that link metabolic dysfunction in order to outline future therapeutic approaches to inflammasome-mediating diseases.
Allergic disorders are exaggerated immune responses to foreign antigens, regardless of the mechanism, while atopic disorders are exaggerated IgE-mediated immune responses (type I hypersensitivity). Allergic dermatitis is a common pathological condition of skin in humans and dogs. Canine allergic dermatitis presents with clinical signs similar to those reported in humans, and its causes are complex; therefore, diagnostic tests and treatments may need to be adjusted for each patient. Dogs with allergic dermatitis can suffer from secondary infections, which must be considered and confirmed or excluded for successful treatment. In this report, 35 cases of canine allergic dermatitis diagnosed using variable methods, including histological and cytological examination, are described. Patients were treated with oral or topical medications (antimicrobials, anti-inflammatories, immune modulators, topical ointments, and medicated shampoos), and their diets and environmental surroundings were also modified. This report provides an analysis of the breed, gender, age of onset, clinical signs, diagnostic methods, and treatments for canine allergic dermatitis. The information on canine allergic dermatitis presented here could be helpful in the study of human cases because these two species often share living spaces, environments, and lifestyles more closely than other animals. However, previous reports have suggested that human and canine allergies differ in some features, such as involvement of histamine in induction of pruritus, and in histopathological characteristics such as cutaneous structures.
In this study, characteristics and immuno-modulatory effects of Weissella cibaria JW15 isolated from Kimchi, traditional Korean fermented food, were examined for investigation of the capacity of potentially probiotic strains. We measured acid, bile, and heat tolerance, adhesive properties to intestinal epithelial cells, and inhibitory activity against pathogens. JW15 could survive at pH 3.0 for 2 hr, but not at pH 2.0. JW15 also showed tolerance to 0.3% oxgall bile salt, and heat tolerance at 70°C and 80°C for 5 min, respectively. Adhesive ability to Caco-2 cells was similar to that of Lactobacillus rhamnosus GG (LGG), a well-known commercial probiotic. JW15 exhibited antimicrobial activities to pathogenic bacteria such as Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, and Salmonella enteritidis. The immuno-modulatory effects of JW15 were compared with those of LGG, a well-known immune enhancer. For analysis, production of nitric oxide (NO), NF-κB (Nuclear factor κB), Interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) was measured. The concentration of NO induced by JW15 was higher than that by LGG at low concentration (1 × 107 cfu/mL). Low and high (5 × 107 CFU/mL) concentration of JW15 induced statistically higher production of NF-κB, IL-1β, and TNF-α than that produced by LGG, respectively. In conclusion, Weissella cibaria JW15 had ability as a probiotic strain, including acid, bile, and heat tolerance, adhesive properties to intestinal epithelial cells, and inhibitory activity against pathogens. In addition, JW15 showed better immuno-modulatory effects than LGG when NO, NF-κB, IL-1β, and TNF-α were measured. According to these results, the characteristics and immunomodulating activity of Weissella cibaria JW15 are suitable for consideration as a potential probiotic.
This study was conducted in order to determine the functionality of mineral-rich salt with lower NaCl and higher mineral contents on blood pressure and lipid metabolism in Dahl salt-sensitive rats. A 1% salt solution was administered to five-week-old male Dahl rats– one normal and three salt groups (Purified salt, sun-dried salt, and bamboo salt) for 15 weeks. On the basis of the salt production process, the sun-dried group was classified into two subgroups: SS1 (2-year) and SS2 (>5-year) depending on the storage period of the mineral-rich salt. The relationships between salt intake and changes in blood pressure, serum lipids, and serum mineral concentrations were then examined. The results showed that intake of SS2, which is stored for five years, and BS (bamboo salt) resulted in continuous delay of the increase in blood pressure and inhibited angiotensin–converting enzyme (ACE) activity. In addition, a significant decrease in the triglyceride level in serum lipids of approximately 30% was observed in the SS2 group compared to the PS (purified salt) group. However, all salt intake groups showed an increase in total cholesterol levels compared to the normal group. The results demonstrate that intake of mineral-rich salt is beneficial for the human body and results in reduced blood pressure and triglyceride levels in serum lipids, however, conduct of more research will be needed in order to explore other functions.
Our previous research on sulfated polysaccharide purified from Ecklonia cava, a brown alga found in Jeju island, Korea, showed that sulfated polysaccharides modulate the apoptotic threshold of intestinal cells, thereby preventing intestinal damage caused by ionizing radiation. In this study, we investigated the ability of sulfated polysaccharide to augment restoration of small intestinal stem cells from γ-ray-induced damage. In our results, sulfated polysaccharide treatment increased the numbers of Ki-67-positive cells as well as inducible nitric oxide synthase (iNOS)-expressing cells in the small intestine compared with those of irradiated only mice. Meanwhile, exposure to irradiation increased the number of paneth cells, which are frequently associated with intestinal inflammation, whereas sulfated polysaccharide treatment reduced the number of paneth cells in the small intestinal crypt. Conclusively, our data suggest that reduction of iNOS-expressing cells and paneth cells in sulfated polysaccharide-treated mice contributes to the inhibition of radiation-induced intestinal inflammation.
The purpose of this study was to identify the composition and organization of lingual tissues underlying the histo-structural change of developing tongue in Korean native goats by light microscopy (LM). Tongues of the fetuses on days 60, 90, 120 and neonate were examined for the morphological development. In the 60-day-old fetuses, the tongue tissues were differentiated into epithelium, lamina propria and muscle layer. Primordia of filiform, conical, lentiform, fungiform and vallate papillae appeared and rudiments of taste bud were observed in the epithelia of the primordia of the gustatory papillae. The dorsal surface of the lingual epithelia showed a weak PAS positive reaction. Collagenous fibers and small blood vessels were shown in the connective tissues. In the 90-day-old fetuses, Von Ebner’s glands were moderately PAS positive while the muscle fibers and connective tissue were strongly positive for PAS. The collagenous fibers increased and came to have a more complex arrangement in the tongue. The muscle fibers were spread out at various directions and developed in striated muscle bundles. In the 120-day-old fetuses, taste buds were observed in the epithelia of the gustatory papillae, and several well-developed tissues visible such as blood vessels, collagenous fibers, muscle fiber bundles and Von Ebner’s glands. In the neonates, many taste buds were found in a transverse section of the vallate papilla. The muscle layers, Von Ebner’s glands, collagenous fibers and blood vessels were more developed than those of the 120-day old fetuses. These findings indicate that goat tongues have a variety of different shapes during prenatal development.
To clarify the role of stem cells in hepatocarcinogenesis, CD44 expression was investigated in mouse livers as well as embryonic cell lineages treated with diethylnitrosamine (DEN). Liver tumors induced by DEN were analyzed by immunohistochemisty for CD44. Liver tissues were sampled at 6, 24, and 48 hr after treatment with saline or DEN. Mouse embryonic stem cells (ESCs), hepatic progenitor cells (HPCs), and hepatocyte like cells (HCs), representing 0, 22, and 40 days of differentiation, respectively, were treated with DEN at four doses (0, 1, 5, and 15 mM, respectively) for 24 hr, after which CD44 expression levels were examined by relative quantitative real-time PCR. CD44 expression was weakly detected in tumor cells as well as in some hepatocytes surrounding the tumor cells. However, CD44 expression was not detected in liver tissue treated with DEN at early time points. The CD44 mRNA expression level was significantly different among cells treated with 5 mM DEN at day 22 (P<0.01) as well as 1, 5, and 15 mM DEN at day 40 (P<0.01) compared with control. Taken together, CD44 expression slightly increased in mouse DEN-induced tumors. Furthermore, expression of CD44 in embryonic cell lineages treated with various doses of DEN significantly differed among embryo stem cells and derived hepatic lineage cells. This suggests that CD44 expression may be modulated in the progeny of stem cells during their differentiation toward hepatocytes, and its expression may increase in the tumor stage but not during early carcinogenesis.
Antimicrobial peptides (AMPs) are an important component of innate defense mechanisms with broad-spectrum activities against various pathogenic microorganisms, including Gram-positive and Gram-negative bacteria, fungi, and viruses. Antibiotic resistance has become a pervasive and global health burden, resulting in the immediate need to develop a new class of antibiotic substances. We screened a 16-mer random peptide library using the yeast two-hybrid system with Beclin 1 as bait and found that two 16-mer peptides (named P4 and P30) appeared to interact with Beclin1 in the β-gal assay. The two candidate cDNAs were introduced into the yeast secretory system of Pichia pastoris and their expression induced in the presence of methanol. Spectrophotometric analysis and Disc clear zone assay using the supernatant of the yeast growth media showed that both of the two peptides had strong activities against Staphylococcus aureus, MRSA (methicillin resistance Staphylococcus aureus), MRSA2242, and MRSA-2250, but no effect on commensal Lactobacillus strains. PCR analysis of the genomic DNA of transformed Pichia pastoris using AOX1 primers revealed that the two cDNAs were integrated into the genome at the AOX1 locus. Our result suggests that these peptides could be developed as a useful alternative to classic chemical antibiotics.
The anti-proliferative efficacy of t,t-conjugated linoleic acid (t,t-CLA), c9,t11-CLA, and t10,c12-CLA was compared in several human cancer cell lines. Gastric NCI-N87, liver Hep3B, pancreas Capan-2, and lung NCI-H522 cancer cells were incubated with 50 μM CLA isomers over a period of 6 days. The t,t-CLA inhibited the growth of all cancer cell lines to different extents, but c9,t11-CLA and t10,c12-CLA inhibited or stimulated the growth of the cancer cell lines. NCI-N87 cells were the most sensitive to growth inhibition and apoptosis from all CLA isomers tested. In NCI-N87 cells, CLA isomers reduced the release of arachidonic acid (AA) via the inhibition of cytosolic phospholipase A2 (cPLA2 ) activity, consequently reducing the production of PGE2 through the inhibition of cyclooxygenase-2 (COX-2). The efficacies of CLA isomers were in the following order (from most to least effective): t,t-CLA, t10,c12-CLA and c9,t11-CLA. Overall, these results imply that the anti-proliferative efficacy of t,t-CLA on cancer cells, especially NCI-N87 cells, was greater than other CLA isomers due to its induction of apoptosis through the inhibition of cPLA2 and COX-2 activities.
This report describes a rare case of primary rectal mature teratoma in a 56-year-old woman. She was referred to the outpatient clinic with a large pedunculated rectal mass, which was found during a regular health check-up. Polypectomy was performed and microscopic findings showed various structures derived from all three germ cell layers. Epidermis, hair follicles, sebaceous glands, eccrine glands, and apocrine sweat glands, with some scattered melanophages and lymphocytes were present as ectodermal derivatives. Smooth muscle fibers, blood vessels, and fibrous and adipose tissues were found as mesodermal derivatives. In addition, thyroid follicles, mucinous glands, and bronchial respiratory epithelium with peribronchial glands were detected as endodermal derivatives. She is healthy and has shown no evidence of recurrence or distant metastasis for 25 months post-surgical resection. Primary rectal teratomas are generally benign and primarily affect women. Therefore, minimally invasive surgical procedures, such as endoscopic polypectomy for a pedunculated polyp and segmentectomy for a larger mass, are satisfactory in most cases. Induction of primary rectal teratomas has been suggested to occur mainly by errors in a single germ cell after the end of meiosis I; in addition, it has also been suggested that the difference in gender incidence may be associated with differences in sex chromosomes between males and females rather than with anatomical proximity between ovary and rectum.