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Journal: Journal of biological regulators and homeostatic agents


Stigmata are one of the most ancient and fascinating mysteries of the Christian religion. The word “stigmata” derives by the Greek “stigma”, that means sign, mark. Classically, stigmata are the sores inflicted on Jesus Christ during his passion and crucifixion. Today, the term stigmatized has been extended to designate several cases of individuals, who show skin sores similar to those of Christ. The Authors report a brief history of stigmata, trying to give an explanation to such a fascinating phenomenon.

Concepts: Religion, Christianity, Jesus, Christ, New Testament, Good Friday, Crucifixion of Jesus, Saint Peter


Collagen Matrix (CM) 10826 is a nanostructured bi-layered collagen membrane obtained from type I and III porcine collagen, which in vitro has shown to have the potential to be a substitute and/or stimulant for soft oral tissue regeneration. The objective of this study was to evaluate the in vivo potential and safety of this membrane for soft tissue regeneration in the early stage of wound healing. Two soft tissue wounds (test and control) were created on the back skin of 5 rabbits (female New Zealand White Rabbits specific pathogen free). All wounds were protected by a special poly-tetra-fluoro-ethylene (PTFE) healing camera. On each rabbit on the test side CM-10826 was used, while on the control side conventional treatment (an autologous pedicle graft) was performed. The healing process was observed clinically after 2 and 6 days, and Magnetic Resonance Imaging (MRI) was performed after this period. After 7 days, animals were sacrificed and specimens were analyzed with light optic microscopy (LM), Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These in vivo trials on rabbits confirmed that CM-10826 is well tolerated, without signs of histological inflammatory reaction and proved to be able to accelerate the spontaneous repair of the skin defect taken as the control. The light-optic and ultra-microscopy of serial biopsies showed that the new matrix is biocompatible and is able to function as a scaffold inducing soft tissue regeneration. In conclusion this study demonstrates that CM-10826 promote early soft tissue regeneration and suggests it is a potential constituent for human autologous keratinocytes seeded derma bioequivalent. It protects the wound from injuries and bacterial contamination accelerating healing process. As a clinical relevance, we consider that the quality of life of patients will be improved avoiding the use of major autologous grafts, reducing the hospitalization time and morbidity.

Concepts: Electron, Wound healing, Collagen, Healing, Magnetic resonance imaging, Wound, Transmission electron microscopy, Scanning electron microscope


This study aimed to explore the protective effect of Lycium barbarum polysaccharides (LBPs) against hyperlipidemia and lipid-induced renal injury in a rat model. Male Sprague-Dawley rats (n=30) were randomly divided into three equal groups: a control group (fed a regular diet) and two experimental groups (fed a high-fat diet). By feeding rats a high-fat diet for 12 weeks, an animal model of hyperlipidemia was established, after which one experimental group received oral LBPs at a dose of 300 mg/kg per day. Blood lipids, renal function, and urinary proteins were measured after 12 weeks. Changes in renal pathology and expression levels of sterol regulatory element binding transcription factor 1 (SREBP-1), interleukin-6 (IL- 6), tumor necrosis factor-alpha (TNF-α), AMP-activated protein kinase (AMPK) were determined. Rats with hyperlipidemia induced by a high-fat diet showed increases in blood lipids and blood urea nitrogen, serum creatinine, and urinary protein, as well as increases in renal levels of SREBP-1, TNF-α, and IL-6 and decreases in renal levels of adiponectin and AMPK. Administration of LBPs restored blood lipid, blood urea nitrogen, serum creatinine, and urinary protein levels, downregulated renal levels of SREBP-1, TNF-α, and IL-6, and upregulated renal levels of adiponectin and AMPK. These results indicate that LBPs may mediate lipid metabolism, enhance anti-inflammatory responses, and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia.


Gastroesophageal reflux disease (GERD) is defined as a “disease that develops when the reflux of stomach contents induces troublesome symptoms and/or complications”. From a therapeutic point of view, many options have been proposed, including proton pump inhibitors (PPI), antihistamines (H2- receptor antagonists), antacid chemical compounds, antireflux barrier (using alginates), prokinetics, inhibitors of gastric sphincters, protection of mucosal tissue, neuromodulators, nociceptor antagonists, lifestyle modification, and surgery. A new medical compound has been recently launched in Italy: Marial® (manufactured by Aurora, Milan, Italy) containing magnesium alginate and E-Gastryal®. The aim of this survey was to analyse the patients’ characteristics and the prescriptive approach considering both the past or current treatments and clinical features during a visit in 56 gastroenterological centers, distributed in the whole of Italy. One thousand eight hundred forty-nine patients (46.5% males, and 53.5% females, mean age 48.59 years) were visited. Patients with positive reflux symptoms index (RSI+) had higher GIS scores than RSI- subjects. PPIs (both as monotherapy or plus add-on) were the most common medication prescribed before the visit. There was a significant change of prescription to Marial® at the visit. More precisely,, Marial® was preferentially prescribed to about a quarter of the patients, particularly to those with lower GIS score, whereas PPI plus add-on option was preferred for patients with higher GIS score. In conclusion, the current experience demonstrated that GERD may be managed considering a patient-centred work-up by using the GIS questionnaire. GIS score may be able to define the medication choice that includes also the new medical compound Marial®.

Concepts: Medicine, Gastroenterology, Stomach, Chemical compound, Gastroesophageal reflux disease, Lansoprazole, Antacid, Gaviscon


Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Virus activate MCs which release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.


COVID-19 (coronavirus disease-19) involves humans as well as animals and may cause serious damage to the respiratory tract including the lung. This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease. When COVID-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1b and IL-6. The binding of COVID-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1b which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1b which is a mediator of lung inflammation, fever and fibrosis. Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections. Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Ra receptor. IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase. This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1β, IL-6, TNF and CCL2. The suppression of IL-1b by IL-37 in inflammatory state induced by COVID-19 can have a new therapeutic effect previously unknown. Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages. IL-38 is also a suppressor cytokine which inhibits IL-1b and other pro-inflammatory IL-family members. IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by COVID-19, providing a new relevant strategy.


CoV-19/SARS-CoV-2 is a highly pathogenic virus that causes coronavirus-19 disease (COVID-19) an acute respiratory distress syndrome which provokes serious problems for global health. Studies suggest that there are many differences between men and women in the immune response to CoV-19 infection and inflammatory diseases. Women, compared to men, are less susceptible to viral infections based on a different innate immunity, steroid hormones and factors related to sex chromosomes. The presence of two X chromosomes in women emphasize the immune system even if one is inactive. The immune regulatory genes encoded by X chromosome in female gender causes lower viral load levels, and less inflammation than in man, while CD4+ T cells are higher with better immune response. In addition, women generally produce higher levels of antibodies which remain in the circulation longer. The levels of activation of the immune cells are higher in women than in men, and it is correlated with the trigger of TLR7 and the production of IFN. TLR7 is higher in women than in men and its biallelic expression leads to higher immune responses and increases the resistance to viral infections. TLR7 is expressed in innate immune cells which recognizes single strand RNA virus by promoting the production of antibodies against the virus and the generation of pro-inflammatory cytokines including IL-6 and IL-1 family members. Moreover, in women the production of inflammatory IL-6 after viral infection is lower than in males and is often correlated with a better longevity. In addition, on the X chromosome there are loci that code for the genes involved in the regulation of immune cells such as FOXP3, and transcription factor for Treg involved in virus pathogenesis. The X chromosome influences the immune system by acting on many other proteins, including TLR8, CD40L and CXCR3 which can be over-expressed in women, and influence the response to viral infections and vaccinations. However, the biallelic expression of the X-linked genes can promote harmful autoimmune and inflammatory responses. Cardiovascular diseases are more frequent in males and subjects without cardiovascular dysfunctions infected by CoV-19 have a better prognosis. ACE2 is a receptor for CoV-19 and protects lung damage. CoV-19 infection and the virus’s Spike protein inhibit the expression of ACE2, abolishing its protective function. Inhibitors of the angiotensin converting enzyme (ACEI) are used to stem the devastating effects of CoV-19, to increase the number of CD3 and CD8 T cells and to reduce the viral load and IL-6 levels that control CoV-19 replication via NF-B, but these effects are still under study. It is hoped that certain drugs, such as CoV-19 receptor blockers, anti-inflammatories (against rheumatic diseases), monoclonal antibodies, anti-IL-1 and anti-IL-6, the remdesevir drug (analogue adenosine, effective against ebola), hydroxychloroquine (for the treatment of malaria) and vaccines, will open up new strategies and new therapeutic ways to combat this terrible virus.


The aim of the multicentre study promoted by Nuova FIO is to evaluate the beneficial effects of the systemic Oxygen-Ozone (O2O3) therapy in patients suffering from SARS COV-2 disease in the early phases of the disease, before worsening, up to the need of tracheal intubation. The study is based on the rationale on that the systemic oxygen-ozone treatment could be effective, positively influencing the disease evolution and/or being able to mitigate the onset of the cytokine storm syndrome at least partially.


Orthopedic temporomandibular joint (TMJ) instability is very common among children and adults. It is often associated with pain in the cervicofacial region, and muscle contraction. To investigate whether muscle contraction can cause permanent posterior rotation of the head and whether treatment with splint and kinetotherapy is efficient, a literature review was carried out of patients with pain in the cervicofacial area. Additionally, the case of a 15-year old patient presenting with permanent posterior rotation of cra¬nium, with no movement between the first two vertebra and pain in the cervicofacial area was reported. Kinetotherapy followed by rapid maxillary expansion improved the function of cervical vertebrae and re¬duced the cervicofacial pain within the first two weeks. Kinetotherapy, rapid maxillary expansion, and or¬thodontic treatment with a stable joint position could be a good therapy to control occipital-atlas function.


Long noncoding RNA (lncRNA) LINC00473 has been reported to be involved in the regulation of several human cancers. However, the regulatory mechanism of LINC00473 is still unknown in lung adenocarcinoma. In this study, RT-qPCR was used to measure the expression of LINC00473, miR-1294 and ROBO1. The functional mechanism of the LINC00473/miR-1294/ROBO1 pathway was investigated by CCK-8, Transwell and dual luciferase reporter assays. The results showed that LINC00473 was up-regulated and miR-1294 was down-regulated in lung adenocarcinoma tissues and cells. LINC00473 can bind to miR-1294, and reciprocal inhibition between LINC00473 and miR-1294 expression was identified in lung adenocarcinoma. Functionally, LINC00473 promoted cell proliferation and motility in lung adenocarcinoma by downregulating miR-1294. In addition, miR-1294 directly targets ROBO1. ROBO1 served as an oncogene in lung adenocarcinoma. In particular, LINC00473 promoted the progression of lung adenocarcinoma by upregulating ROBO1. In conclusion, LINC00473 acts as a tumor promoter in lung adenocarcinoma by regulating the miR-1294/ROBO1 axis.