Regenerative medicine of pancreatic islets

The pancreas became one of the first objects of regenerative medicine,since other possibilities of dealing with the pancreatic endocrine insufficiency were clearly exhausted.The number of people living with diabetes mellitus is currently approaching half a billion,hence the crucial relevance of new methods to stimulate regeneration of the insulin-secretingβ-cells of the islets of Langerhans.Natural restrictions on the islet regeneration are very tight;nevertheless,the islets are capable of physiological regeneration viaβ-cell self-replication,direct differentiation of multipotent progenitor cells and spontaneousα-toβ-orδ-toβ-cell conversion(trans-differentiation).The existing preclinical models ofβ-cell dysfunction or ablation(induced surgically,chemically or genetically)have significantly expanded our understanding of reparative regeneration of the islets and possible ways of its stimulation.The ultimate goal,sufficient level of functional activity ofβ-cells or their substitutes can be achieved by two prospective broad strategies:β-cell replacement andβ-cell regeneration.The“regeneration”strategy aims to maintain a preserved population ofβ-cells through in situ exposure to biologically active substances that improveβ-cell survival,replication and insulin secretion,or to evoke the intrinsic adaptive mechanisms triggering the spontaneous non-β-toβ-cell conversion.The“replacement”strategy implies transplantation ofβ-cells(as non-disintegrated pancreatic material or isolated donor islets)orβ-like cells obtained ex vivo from progenitors or mature somatic cells(for example,hepatocytes orα-cells)under the action of small-molecule inducers or by genetic modification.We believe that the huge volume of experimental and clinical studies will finally allow a safe and effective solution to a seemingly simple goal-restoration of the functionally activeβ-cells,the innermost hope of millions of people globally.

Molecular pathways of liver regeneration:A comprehensive review

The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70%of its volume.Although knowledge of this phenomenon dates back to Greek mythology(the story of Prometheus),many aspects of liver regeneration are still not understood.A variety of different factors,including inflammatory cytokines,growth factors,and bile acids,promote liver regeneration and control the final size of the organ during typical regeneration,which is performed by mature hepatocytes,and during alternative regeneration,which is performed by recently identified resident stem cells called“hepatic progenitor cells”.Hepatic progenitor cells drive liver regeneration when hepatocytes are unable to restore the liver mass,such as in cases of chronic injury or excessive acute injury.In liver maintenance,the body mass ratio is essential for homeostasis because the liver has numerous functions;therefore,a greater understanding of this process will lead to better control of liver injuries,improved transplantation of small grafts and the discovery of new methods for the treatment of liver diseases.The current review sheds light on the key molecular pathways and cells involved in typical and progenitor-dependent liver mass regeneration after various acute or chronic injuries.Subsequent studies and a better understanding of liver regeneration will lead to the development of new therapeutic methods for liver diseases.

Rare primary mature teratoma of the liver:A case report

BACKGROUND Primary liver teratoma is an extremely rare tumor usually affecting children under the age of 3 years.Specific signs of teratoma on ultrasound,computed tomography(CT)or magnetic resonance imaging are lacking,which makes morphology the only diagnostic tool.Misdiagnosis of a mature teratoma may lead to excessive liver resection,whereas misdiagnosis of an immature teratoma may result in spread,causing a life-threatening condition.Consequently,a careful tumor examination is important,and the rarest types of tumors must be accounted for.CASE SUMMARY We describe a 52 years old female who presented with a solid mass in the left liver lobe.Contrast-enhanced CT and magnetic resonance imaging(MRI)revealed a round,heterogeneous lesion containing a number of fluid areas and areas of calcification in the middle,and the provisional diagnosis was cholangiocarcinoma.The patient underwent resection of liver segment I.Immunohistochemistry analysis of the resected lesion indicated thyroid follicular epithelium;however,the thyroid gland was intact.10 years prior to presentation the patient underwent a surgery due to mature teratoma of the right ovary,nevertheless the tumor was benign and could not spread to the liver,in addition teratoma of the liver was also benign.This led to the final diagnosis of primary mature liver teratoma.CONCLUSION Primary hepatic teratoma,including heterotopia of the thyroid gland in the liver,is an extremely rare condition in adults that needs to be considered in the differential diagnosis of solid-cystic neoplasms in the liver and cholangiocarcinoma.This case adds to the limited literature on the patient presentation,clinical workup and management of liver teratomas.

Immediate, Fast, and Overcome Response of the Organism in Response to Energy Osteopathy on the Model of Primary Gonarthrosis (Polyparametric and Statistical Studies)

In 26 patients with confirmed primary verified gonarthrosis(PGA),a clinical and instrumental examination was conducted to evaluate the response energy osteopathy followed by statistical processing of the data.Three types of the body’s response to treatment were identified:immediate,fast,and delayed,which,despite the different informative value of the data of the polyparametric study,allowed judging the effectiveness of the method used.

Beneficial Effects of Non-chemically Grown Traditional Rice/Rice Based Functional Food(NGTRF)in Nutritional Management of Nafld and Diabetes Mellitus

Non-communicable diseases(NCDs)are commonly associated with non-alcoholic fatty liver/non-alcoholic fatty liver disease(NAFL/NAFLD)for which no drugs or specific food are available either to control or to cure.We encounter promising results with NGTRF in nutritional Management of NAFLD and diabetes.Objective is to compare the effect of using NGTRF over routine western management(RWM)and Hela Nila Wedakama(HNW)patients with NCD,including metabolic syndrome,are prescribed NGTRF(produced by Hela Suwaya)and followed up.The five therapeutic categories are(1)RWM alone;(2)NGTRF alone;(3)NGTRF+RWM(in Galle);(4)NGTRF+RWM(in Gampaha);(5)NGTRF+RWM+HNW.According to clinical,biochemical and radiological profiles,majority of categoroes 2,3,4 and 5 are either controlled or cured effectively and sustainably compared to category 01.Preliminary evidence shows that effectiveness and sustainability of prescribing NGTRF is better.According to“Hela Suwaya”knowledge,genetic basis of food(conventional vs.traditional)and agronomic practices should be strongly considered while prescribing food.Traditional rice grown with toxin free Hela Suwaya“Hela Govithena”technology improves the micronutrient,prebiotic,probiotic and antioxidant profiles of food.Agrochemical farming reduces these parameters by reducing soil pH and biota.Functional foods produced by Hela Suwaya post-harvest food technology(such as rice-based porridge)will further improve these nutritional profiles.The resulting optimization of the disturbed liver function is the key factor behind this beneficial effect on whole NCD spectrum.This is observed as cured or reduced NAFL/NAFLD.We have already planned controlled clinical trials for further confirmation.Proper food-based intervention is therefore strongly suggested.

Left atrial appendage occluder implantation for stroke prevention in elderly patients with atrial fibrillation： acute and long-term results

Atrial fibrillation （AF） is the most common cardiac ar-rhythmia in clinical practice with an increasing incidenceand prevalence. With ageing, the risk of thromboembolicand hemorrhagic events increases dramatically. As it hasbeen reported previously, 3-year survival rate among pa-tients with AF over 75 years of age after stroke is less than50%, and almost 90% of those patients will remain dis-abled.

Multipotent stromal cells stimulate liver regeneration by influencing the macrophage polarization in rat

AIM To investigate the influence of the umbilical cordderived multipotent stromal cells(MSCs) on recovery of the liver after the subtotal resection, that is, removal of 80% of the organ mass, a renowned model of the small-for-size liver remnant syndrome. METHODS The MSCs were obtained from the intervascular tissue of umbilical cords, dissected from rat fetuses, by the explant culture technique. The vital labeling of MSCs with РКН26 was carried out on the 3 rd passage. The subtotal resection was performed on male Sprague-Dawley rats. The experimental group animals received a transplant 106 MSCs infused into the spleen. Hepatocyte proliferation was assessed by counting of either mitotic figures or Ki67-positive cells in microscopic images. MSC differentiation was assessed with antibodies to hepatocyte-specific marker cytokeratin 18(CK18), cholangiocyte-specific protein CK19, smooth muscle cell-specific protein α-SMA, the endothelial cell marker CD31, or the active fibroblast marker FAPα. Total macrophages of the liver were selectively stained in cryosections incubated with antiCD68 antibodies(1:100, Abcam), while the M2 a and M2 c macrophage populations were selectively stained with anti-CD206 antibodies. Expression of interleukin and growth factor genes was evaluated with PCR-RT.RESULTS Intrasplenic allogeneic transplantation of the umbilical cord-derived multipotent stromal cells stimulates reparative processes within the residual liver tissue after subtotal resection(removal of 80% of the organ mass), as indicated by increased rates of hepatocyte proliferation and accelerated organ mass recovery. These effects may result from paracrine influence of the transplanted cells on the resident macrophage population of the liver. The transplantation favors polarization of macrophages to M2 phenotype(the M2-polarized macrophages specifically express CD206; they are known to suppress inflammation and support tissue repair). No differentiation of the transplanted cells into any of the liver cell types have been observed in the study.CONCLUSION We found no direct evidence for the paracrine effect of MSCs on liver regeneration after the subtotal liver resection in rats. However, the paracrine mechanism of the therapeutic activity of transplanted MSC is indirectly indicated by a decrease in the total number of CD68 + macrophages and an increase in the proportion of M2 pro-repair macrophages in the regenerating liver as compared to animals in which the transplantation was only mimicked.

Public knowledge,practices and perceptions on typhus fevers in Southern Sri Lanka

Objective:To assess public knowledge,practices and perceptions on typhus fevers in Sri Lanka.Methods:A descriptive study was done in four selected typhus-prone areas in Southern Sri Lanka.A mixed-method was employed using face-to-face interviews and questionnaire-based surveys among confirmed cases of typhus and at-risk populations,respectively.Frequencies,percentages,and means were used to characterize socio-demography and evaluate disease awareness.Results:The lay terms for typhus fevers reported in the studied region were“peacock fever”,“tick fever”and“bird fever”.A total of 499 subjects participated[mean±SD,(45±16)years]in the questionnaire-based survey,and 13.6%(n=68)reported past experience of typhus fever,1.2%(n=6)identified the disease as“typhus”while 58.7%(n=293)and 11.8%(n=59)knew it as‘peacock fever’and‘tick fever’,respectively.The etiological agent was unknown to 95.2%(n=475),but 53.5%(n=267)were aware that it was vector-borne.Fever(57.3%,n=286),eschar(35.7%,n=178),headache(22.0%,n=267)and myalgia(19.2%,n=96)were identified as key symptoms.Past disease experience was significantly associated with higher awareness of the main disease symptoms(fever:χ^(2)=15.713,P<0.001;headache:χ^(2)=19.447,P<0.001;lymphadenopathy:Fisher’s exact test,P=0.023;eschar:χ^(2)=12.049,P<0.001).None knew of any disease prevention methods.Participants with a past history of typhus fever had sought treatment at state hospitals(55.9%,38/68)and private sector hospitals(5.9%,4/68).Conclusions:Public awareness on preventive practices for typhus fevers was rare among the participants though vector-borne aspect was known to many.Clinical disease awareness was deficient among those without past experience of typhus fever.Community sensitization on vector avoidance strategies is highly recommended.

Regional deprivation and cause-specific mortality in Russian adults in 2006-2022

Objective:The relationship between cause-specific mortality and regional socio-economic and environmental indicators remains poorly studied in Russia.The study first aims to study regional differences in cause-specific mortality among the population aged 20 years and older in Russia,and second to investigate the association between regional deprivation and cause-specific mortality.Material and methods:Russian deprivation index was used to measure level of deprivation.The index consists of three components:social,economic and environmental.The index measures general deprivation,and its compo-nents measure social,economic and environmental deprivation.The mortality data by age(five-year groups)and sex in the subjects of Russia from 2006 to 2022 were extracted from the Russian Fertility and Mortality Database of the Center of Demographic Research of the New Economic School.Results:In the most general deprived areas,mortality rate from infectious and parasitic diseases increased by more than twice in the total population,women and men as compared to the least deprived quantile(Q1).Fully adjusted negative binomial regression showed an increase in mortality rate from injuries,poisoning and external causes and infectious and parasitic diseases in more social deprived areas as compared to Q1 in the total population,women and men.In men,there was a significantly higher mortality rate from neoplasms and from infectious and parasitic diseases in more economic deprived areas as compared to Q1.Both in total population and in women,there was a trend towards an increase in mortality from neoplasms depending on the level of environmental deprivation.Conclusions:This is the first study examining the relationship of contextual factors with cause-specific mortality that takes into account sex,age and year of death at the population level in Russia.General,social,economic and environmental deprivation are associated with cause-specific mortality.

Supratentorial dural-based collision of cavernoma and meningioma: a case report

Background: Collision tumor is a very rare case of cerebral lesion. Approximately 50 reports of intracranial collision tumors were described in the literature. We present a case of supratentorial dural-based convexity collision tumor radiologically mimicking cavernous malformation and composed of cavernous malformation and meningioma. Case presentation: The case presents a 63-year-old female having MR findings such as hemorraged supratentorial dural-based mass with 'popcorn' signs and hemosiderin deposits. The patient underwent craniotomy and evacuation of the subdural hematoma with resection of the tumor mass. Histologically the lesion had signs of a cavernoma and meningioma. MRI in a year after surgery did not reveale residual tumor mass or recurrence. Conclusions: Collision tumor is a very rare case. Preoperative diagnosis of a dural lesion is difficult and challenging. A neuroradiological differential diagnosis of similar cases needs focused attention.

The Usefulness of Zhukovsky Double Balloon in Obstetric Hemorrhage

Objective:To evaluate the effectiveness of the use of a modified Zhukovsky double(vaginal and uterine)balloon to improve the results of treatment in women with obstetric hemorrhage.Methods:We conducted an observational controlled study including 701 puerperas,which were divided into two groups:The main group consisted of 508 women,who underwent a combined management,that is,traditional(transfusion of fresh frozen plasma,erythrocyte mass,uterotonics,hemostatic agents),surgical hemostasis in cases of caesarean section,and insertion of a double Zhukovsky balloon;while the comparison group included 193 patients,who were managed traditionally.The main group and the comparison group were divided into subgroups according to the main etiology of obstetric hemorrhage:ⅠA andⅠB-postpartum;ⅡA andⅡB-placenta accreta;ⅢA andⅢB-postpartum hysterectomy.Results:The most frequent causes of massive obstetric hemorrhage were atony of the uterus(39.2%),placenta previa(29.1%),and placental abruption(11.5%).Of the 508 balloon insertions,345(70.7%)were inserted for hemorrhage during cesarean section and 148(29.3%)for obstetric hemorrhage after spontaneous delivery.Among the obstetric hemorrhage at caesarean section,lower segment bleeding prevailed(78.1%),caused mainly by placenta previa,placenta accreta,placental abruption,polyhydramnios,and uterine scar defects.Combined management,including surgical hemostasis and insertion of vaginal and uterine balloon of Zhukovsky,reduced blood loss by 1.5 times and the number of hysterectomies by 6.72 times compared to controls.Conclusion:The use of a modified Zhukovsky double balloon in the management of obstetric hemorrhage may reduce the number of hysterectomies and the amount of blood loss.