Sustained release of Lactobacillus casei cell wall extract can induce a continuous and stable IgA deposition model.

Mucosal immune regulation is considered a key aspect of immunopathogenesis of IgA nephropathy (IgAN). Direct experimental evidence clarifying the role of intestinal mucosa attributes in IgAN is lacking. In this study, a mouse model was established via multiple low-dose intraperitoneal injections of Lactobacillus casei cell wall extract (LCWE) emulsified with Complete Freund's Adjuvant (CFA). We found continuous and stable deposition of IgA in glomerular mesangial areas, accompanying high circulating levels of IgA and IgA-IgG complexes. Expression of the key extracellular matrix components collagen IV and fibronectin also increased in the mesangial areas of LCWE-induced mice. IgA+ B220+ B-cell proportion increased in the small intestine (SI), Peyer's patches, inguinal lymph nodes, spleen, and bone marrow. The intestinal barrier was dysfunctional in the LCWE-induced mice, and consistent with this, higher levels of serum zonulin (namely prehaptoglobin-2), a regulator of epithelial and endothelial barrier function, were observed in patients with IgAN. Hematoxylin and eosin staining results indicated that immune tissues such as liver, spleen, and lymph nodes showed an inflammatory response and focal lesions. Glucocorticoid methylprednisolone treatment could alleviate serum IgA and IgA-IgG complex levels and mesangial IgA deposition. Taken together, our results indicate that we have successfully constructed a mouse model with IgA deposition in the mesangial areas of the glomeruli and provide evidence for the connection between the intestinal barrier and elevated circulating IgA and IgA-IgG in IgAN. © 2022 The Pathological Society of Great Britain and Ireland.

Chaga ( Inonotus obliquus), a Future Potential Medicinal Fungus in Oncology? A Chemical Study and a Comparison of the Cytotoxicity Against Human Lung Adenocarcinoma Cells (A549) and Human Bronchial Epithelial Cells (BEAS-2B).

BACKGROUND: Inonotus obliquus, also known as Chaga, is a parasitic fungus growing on birches and used in traditional medicine (especially by Khanty people) to treat various health problems. In this study, we aimed to quantify the 3 metabolites frequently cited in literature, that is, betulin, betulinic acid, and inotodiol in the Chaga recently discovered in forests located in Normandy (France), and to compare their concentrations with Ukrainian and Canadian Chaga. This study also explores the cytotoxicity of the French Chaga against cancer-derived cells and transformed cells. METHODS: A quantification method by HPLC-MS-MS (high-performance liquid chromatography-tandem mass spectrometry) of betulin, betulinic acid, and inotodiol was developed to study the French Chaga and compare the concentration of these metabolites with extracts provided from Chaga growing in Canada and Ukraine. This method was also used to identify and quantify those 3 compounds in other traditional preparations of Chaga (aqueous extract, infusion, and decoction). Among these preparations, the aqueous extract that contains betulin, betulinic acid, and inotodiol was chosen to evaluate and compare its cytotoxic activity toward human lung adenocarcinoma cells (A549 line) and human bronchial epithelial cells (BEAS-2B line). RESULTS: French Chaga contains betulin and betulinic acid at higher levels than in other Chaga, whereas the concentration of inotodiol is greater in the Canadian Chaga. Moreover, the results highlighted a cytotoxic activity of the Chaga's aqueous extract after 48 and 72 hours of exposure with a higher effect on cancer-derived cells A549 than on normal transformed cells BEAS-2B ( P = 0.025 after 48 hours of exposure and P = 0.004 after 72 hours of exposure).

[Effectiveness of pidotimod in combination with bacterial lysates in the treatment of the pfapa (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome]. / Efficacia del Pidotimod in associazione a lisato batterico nel trattamento della syndrome PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis).

AIM: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome is the most common autoinflammatory syndrome in pediatrics, accepted as an hyperimmune condition. Pidotimod is a molecule with immunomodulatory activity on both innate and adaptive immune responses; it also has the capacity to modulate the function of the respiratory epithelial cells through the activation of a NK-KB pathway which would involve the host-virus interaction. Moreover, the proven beneficial effect of Pidotimod in enhancing the immune response during vaccination, and its benefits in the prevention of respiratory tract infections, should be noted. METHODS: A joint combination of Pidotimod and bacterial lysates was used to treat 37 children with a clinical diagnosis of PFAPA; within the end of the first year of therapy, the healing rate of PFAPA symptoms was 67.5% (25 children), with a 10.8% (4 cases) still in complete remission within the end of the second year of follow-up. RESULTS: It is important to highlight that 29 children (78.3%) had benefitted from this therapy, in terms of healing, with a marked decrease in the incidence of fever from a total of 360 to 106 episodes, and episodes of periodic fever occurring almost 4 times less frequently. The use of Pidotimod determined a significant reduction of surgical tonsillectomy's treatment. CONCLUSION: This approach had a strong impact on the children's quality of life; a significant decrement in the use of antipyretic drugs, as well as a lower rate of antibiotic prescription, were also noted. It also had a dramatic impact on families' lives, because the treatment lowers the number of absences of family members from work or school/kindergarten.

Immunostimulatory properties and antitumor activities of glucans (Review).

New foods and natural biological modulators have recently become of scientific interest in the investigation of the value of traditional medical therapeutics. Glucans have an important part in this renewed interest. These fungal wall components are claimed to be useful for various medical purposes and they are obtained from medicinal mushrooms commonly used in traditional Oriental medicine. The immunotherapeutic properties of fungi extracts have been reported, including the enhancement of anticancer immunity responses. These properties are principally related to the stimulation of cells of the innate immune system. The discovery of specific receptors for glucans on dendritic cells (dectin-1), as well as interactions with other receptors, mainly expressed by innate immune cells (e.g., Toll-like receptors, complement receptor-3), have raised new attention toward these products as suitable therapeutic agents. We briefly review the characteristics of the glucans from mycelial walls as modulators of the immunity and their possible use as antitumor treatments.

Polysaccharide-rich fraction of Termitomyces eurhizus accelerate healing of indomethacin induced gastric ulcer in mice.

The current study aims to determine the healing activity of water soluble polysaccharide-rich fraction of a wild mushroom, Termitomyces eurhizus (TEps) against the indomethacin induced gastric ulceration in mice model. Gastric tissue histology, myeloperoxidase (MPO) activity, cyclooxygenases (COX) 1 and 2 expression, prostaglandin E2 (PGE2) synthesis, and modulation of pro/anti inflammatory cytokines expression were studied for this purpose. Histological study shows that TEps (20 mg/kg) effectively healed the gastric ulceration. Based on biochemical results, the healing capacities of TEps could be attributed to reduction of MPO activity and protection of mucosal mucin content. Enhanced synthesis of PGE2 by modulation of COX-1 and COX-2 expression and a prominent shift of cytokines expression from pro (TNF-α, IL-1ß) to anti inflammatory (IL-10) side are also held responsible for ulcer healing. The preliminary study highlights the anti-ulcerogenic property of polysaccharide-rich fraction of Termitomyces eurhizus and opens an alternative cure for NSAID induced gastroduodenal diseases.

Phellinus baumii ethyl acetate extract alleviated collagen type II induced arthritis in DBA/1 mice.

Mushrooms have a long history of dietary benefits in Asia due to their health-promoting effects. Phellinus baumii, a wild mushroom, has been reported to have anti-platelet, anti-inflammatory, anti-obesity and free radical scavenging activities. However, its anti-rheumatoid arthritis (RA) property remains poorly understood. Hence, we investigated the protective effect of Phellinus baumii ethyl acetate extract (PBEAE) against bovine collagen type II induced arthritis (CIA) in DBA/1 mice. PBEAE (50 and 150 mg/kg) reduced the CIA score and leukocyte count in draining lymph nodes (DLNs) and inflamed joints. PBEAE also attenuated the expressions of CD3⁺ (T cells), CD19⁺ (B cells), CD4⁺ (T-helper), CD8⁺ (T-cytotoxic), MHC class II/CD11c⁺ (antigen-presenting cells), double positives (B220⁺/CD23⁺ and CD3⁺/CD69⁺: early lymphocyte activation markers) and CD4⁺/CD25⁺ (activated T-helper) leukocyte subpopulations in DLNs. Likewise, CD3⁺ and Gr-1⁺CD11b⁺ (neutrophil) counts in inflamed joints were also decreased. Furthermore, PBEAE reduced the serum levels of anti-collagen type immunoglobulin G, tumor necrosis factor-α and interleukin (IL)-1ß and IL-6. Taken together, PBEAE impaired cellular recruitment to the inflamed joint and alleviated CIA, and thus could be considered as a potential agent against rheumatoid arthritis.

Characterization and antineoplasic effect of extracts obtained from Pleurotus sajor-caju fruiting bodies.

Fungi of the Pleurotus genus present a great industrial interest due to their possibility of producing pharmacological compounds, pigments, aromas, organic acids, polysaccharides, enzymes, vitamins, amino acids, etc. Among the therapeutic products, we can highlight those with antineoplasic activity, attributed to the fungi cell wall components. Based on this, the objective of this work was to study the antineoplasic capacity of the polysaccharidic fractions obtained from Pleurotus sajor-caju fruiting bodies. Female Swiss mice were inoculated with the Ehrlich ascitic tumor (5 x 10(6) cells/animal) in ascitic form. The polysaccharidic fractions were administered intraperitoneally, during a 6-day period. Fractions FI and FII presented a lower volume of ascitic liquid (3.1 and 1.8 mL, respectively) and a higher reduction in the number of neoplasic cells present in the ascitic liquid (86.2% and 85%, respectively), when compared to the positive control (group inoculated with the tumor but without treatment). These fractions were characterized in terms of monosaccharide composition. Glucose was the major component detected, followed by galactose and mannose. The anomeric carbon configuration of the beta-glucan was confirmed by the (13)C NMR (delta 103.7). Substituted and free C3 and C6 were also detected. Protein bands were confirmed through infrared analysis.

Natural products as aromatase inhibitors.

With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purposes (e.g., botanical dietary supplements) may also afford AIs with reduced side effects. A thorough review of the literature regarding natural product extracts and secondary metabolites of plant, microbial, and marine origin that have been shown to exhibit aromatase inhibitory activity is presented herein.

Taiwanofungus camphoratus activates peroxisome proliferator-activated receptors and induces hypotriglyceride in hypercholesterolemic rats.

Taiwanofungus camphoratus (T. camphoratus), a fungus and a Taiwan-specific, well-known traditional Chinese medicine, has long been used to treat diarrhea, hypertension, itchy skin, and liver cancer. To gain a large amount of T. camphoratus, several culture techniques have been developed, including solid-state culture and liquid-state fermentation. Peroxisome proliferator-activated receptor gamma (PPARgamma) has been described as a hypoglycemic agent that increases insulin sensitivity in peripheral tissues and results in reduced blood glucose, insulin, and triglyceride levels in insulin-resistant animals and in type-2 (non-insulin-dependent) diabetic patients. In this study, we investigate the possibility that T. camphoratus might activate PPARgamma in vitro and hypolipidemic activity in vivo. The results show that an aqueous extract of the wild fruiting bodies of T. camphoratus was able to increase the PPARgamma activity in cells transfected with the PPARgamma expression plasmid and the AOx-TK reporter plasmid. Based on the cell experiment, we examined the hypolipidemic effect of wild fruiting bodies (WFT) and a solid-state culture (SST) of T. camphoratus on SD rats fed on a high-cholesterol (HC) diet. The results show that WFT significantly decreased the serum triglyceride level, but could not affect the cholesterol level. SST only slightly decreased the serum triglyceride level. In addition, both WFT and SST significantly decreased the serum alanine transaminase (ALT) level and protected against the liver damage induced by the HC diet from the results of a histological examination. These results suggest that T. camphoratus might contain PPARgamma ligands and result in a hypotriglyceridemic effect, and that it also exhibits a liver protective activity.

Silent reflux: ex juvantibus criteria for diagnosis and treatment of laryngeal disorders.

CONCLUSIONS: Some primary laryngeal pathologies with specific clinical presentation may be related to silent laryngeal reflux. An ex adjuvantibus proton pump inhibitor (PPI) treatment may be helpful for showing evidence of such a hidden laryngeal disorder. OBJECTIVE: To assess the validity of PPI as an ex adjuvantibus criterion for diagnosis and treatment of suspected reflux-associated laryngitis. PATIENTS AND METHODS: Sixty patients with clinical suspicion of laryngo-pharyngeal reflux (LPR) were identified on the grounds of laryngeal symptoms (dysphonia, cough, globus sensation, increased throat clearing, bad taste, and laryngeal spasm), laryngeal features (arytenoid edema/erythema, partial or total vocal fold erythema, and posterior glottic edema) with or without gastro-esophageal reflux disorder (GERD). They were consequently subdivided in three groups: type I, with LPR symptoms and features without GERD; type II with LPR symptoms and features with GERD; and type III with LPR features only. Types I and III were randomly treated with omeprazole (group A) or with immunostimulating vaccine (group B) for 3 months. Pre- and post-treatment laryngeal features and symptoms in all groups were evaluated by laryngo-stroboscopy and analyzed for statistical correlation. RESULTS: All omeprazole-treated patients showed improvement of laryngeal features and symptoms. With PPI treatment, a more significant improvement was noticed with respect to nonspecific immunostimulant therapy. Also, patients without LPR symptoms showed improvement of laryngeal features.

Extracts of Phellinus gilvus and Phellinus baumii inhibit pulmonary inflammation induced by lipopolysaccharide in rats.

Compared to saline-challenged rats, rats exposed to 50 microg intratracheal lipopolysaccharide showed an increase of total white cells (from 0.3 x 10(6) to 2.4 x 10(6)), neutrophils (from 0.09 x 10(6) to 1.8 x 10(6)), the levels of tumor necrosis factor (TNF)-alpha (from 200 pg ml(-1) to 1200 pg ml(-1)), and interleukin (IL)-1beta (from 220 pg ml(-1) to 650 pg ml(-1)) in the bronchial lavage fluid. However, after pretreatment with extracts of Phellinus gilvus and Phellinus baumii, the total white cells, neutrophils, and the level of IL-1beta in lipopolysaccharide-challenged rats were similar to those in saline-challenged rats, except for TNF-alpha. The results indicate that extracts of P. gilvus and P. baumii may be useful in preventing acute pulmonary inflammation in human diseases.

Studies on the preventive effect of Spirulina maxima on fatty liver development induced by carbon tetrachloride, in the rat.

The aim of the present work was to assess if the feeding of either the oil extract of Spirulina maxima or of its defatted fraction would prevent fatty liver development, induced in rats by a single intraperitoneal dose of carbon tetrachloride (CCl4). Liver and serum lipids were evaluated 4 days after treatment with this agent. Concentration of liver lipids did not differ in rats fed on a purified diet either without or with one of the fractions of Spirulina, except for total cholesterol, which showed a slight increase in the group receiving the oil extract of Spirulina. However, after CCl4 treatment, liver total lipids and triacylglycerols were significantly lower in rats fed on a diet containing any fraction of Spirulina (defatted or the oil fraction) than in rats without Spirulina in their diet. Furthermore, the increased liver cholesterol values, induced by CCl4 treatment, were not observed in rats receiving Spirulina. In addition, rats receiving whole Spirulina in their diet and treated only with the vehicle showed an increase in the percentage of HDL values. The changes in VLDL and LDL induced by CCl4 treatment were not observed in the whole Spirulina group. Furthermore, after CCl4 treatment the values of the liver microsomal thiobarbituric acid-reactive substances were lower in the whole Spirulina group than in the control group. These results support the potential hepatoprotective role of Spirulina.

[Alternatives to steroid therapy in chronic uveitis]. / Alternativen zur Steroidtherapie bei der chronischen Uveitis.

In a search for alternative therapeutic methods other than corticosteroids and cytostatics, the effect of a dialyzable leukocyte extract (DLE), the antimetabolite 5-fluorouracil and the immunosuppressive agent cyclosporin A in corticosteroid-resistant idiopathic uveitis was studied. When DLE was administered to 26 patients who had uveitis forms with exogenous triggering (e.g., infection), as well as forms with an autoimmune background, there was a reduction in the number and duration of recurrences and a statistically proven prolongation of the inflammation-free intervals. This was particularly true in anterior and posterior uveitis and to a lesser extent in the intermediate form. No side effects were observed. 5-Fluorouracil, injected subconjunctivally, is indicated in intermediate uveitis with marked vitreous infiltration and beginning proliferation. Corneal erosion occurs relatively often. During treatment with cyclosporin A (low dose, 5 mg/kg of body weight per day), 14 of 17 patients (9 with intermediate uveitis, 6 with retinal vasculitis, 1 with sympathetic ophthalmia, 1 with panuveitis) showed improved results; in 2 cases the findings remained stationary and only 1 case had low-grade deterioration. If one takes into consideration the fact that in this patient any therapy would have failed, the results are convincing. This is particularly true of retinal vasculitis. There is no effect in cases of central hemorrhagic chorioretinopathy. So far, there have been no serious side effects.

[Controversial and so-called alternative therapeutic approaches]. / Umstrittene und sogenannte ausserschulische Therapieansätze.

In spite of intensive research, it has not yet been possible to produce a complete explanation of the aetiology and pathology of rheumatoid arthritis (R.A.). Therapeutic measures are possible in many phases of the pathogenetic concept, and often produce good, modifying results, improving the course of the disease. No causal therapy of R.A. exists--we do not know the aetiology of this disease. Frustration with conventional medicine on the one side, and the predominating spirit of the times on the other--back to biological methods and the old forms of therapy--are the reasons why chronic polyarthritics drift into the sphere of para-medicine. In the judgement of para-medical methods, "risk/benefit relationship", "superfluous and no longer up-to-date", "controversial--absence of scientific evidence", "controversial", and "controversial--not scientifically acceptable" present some of the decision criteria. Treatment with mussel extracts, beta-sitosterins, THX, and substitution with various substances, as well as anthroposophically-oriented high-potency homeopathy, are to be allocated to the "controversial--not scientifically acceptable" category. If one weighs up the "risk/benefit relationship" of cell therapy, this treatment concept also cannot be supported. Moreover, precisely documented scientific results of this form of therapy do not exist. Methods standing on scientifically-hypothetically interesting ground, but which were tested on too small a group and cannot yet be accepted as sufficiently proven, are therapy with Vitamin E, the use of Thymopoietin, in which, for example, dose-finding and mode of application are not yet firmly established, and therapy with enzyme mixtures. Interferon results, initially extolled in the lay press, have not been confirmed in the most recent studies. Thymopoietin treatments, via the laborious road to the correct application (oral, subcutaneous, intramuscular, intravenous as bolus, intravenous--fractionated), show encouraging successes. As tissue-localized immune complexes (which sort?) play a role in the pathogenesis of R.A., but enzyme mixtures, apart from the problems of absorption, only influence circulating immune complexes, and moreover, in many diseases neither the aetiology nor the pathogenesis is connected with the immune complexes, this therapy concept can be regarded neither as causal nor as scientifically guaranteed. In summary: from the start-point that healing is the ideal aim, it has been forgotten that there are many human sufferings which medicine can ease and ameliorate, but not yet cure.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of glutaraldehyde-modified timothy grass pollen extract in nasal hyposensitisation treatment of hay fever.

12 patients suffering from grass pollen hay fever were treated for 14 weeks pre- and co-seasonally by intranasal self-administration of an aqueous solution of a glutaraldehyde-treated timothy grass pollen allergen. These patients had a statistically significant decrease in nasal symptom scores during the grass pollen peak period and in nasal challenge end-point titre after the season compared to placebo-treated patients. No significant effect was seen on the eye symptoms. 1 patient withdrew from the trial as a consequence of too strong local nasal reactions during treatment. Most other patients treated with active material reported mild local reactions during the first minutes after administration of the nasal spray. In the actively treated group a significant increase in serum and nasal secretion of grass pollen specific IgE, IgG and IgA antibodies was obtained during the treatment. In contrast, in the placebo group a significant increase in IgE antibody levels in serum and secretion occurred during the pollen season. The reduction in symptoms and increase in antibody production together with the simplicity of the procedure makes this approach to immunotherapy attractive.