Degeneration Of Organs Research Articles

Potentially Inappropriate Medication among Older Patients Who Are Frequent Users of Outpatient Services.

Aging is accompanied by changes in organ degeneration, and susceptibility to multiple diseases, leading to the frequent occurrence of adverse drug reactions resulting from polypharmacy (PP) and potentially inappropriate medications (PIM) in older patients. This study employs a retrospective cohort design and investigates the association of PP with PIM among older patients with high rates of medical utilization. Using records from a national pharmaceutical care database, an experimental group is formed from patients meeting these criteria, who are then offered home pharmaceutical care. Correspondingly, a control group is formed by identifying older patients with regular levels of use of medical services who had been dispensed medications at community pharmacies. Multivariate logistic regression is performed to assess the association between the rate of PIM and variables, including age, gender, and PP. The study finds that experimental PP participants had a higher rate of PIM prescription (odds ratio (OR) = 5.4) than non-PP control participants (all p < 0.001). In clinical practice, additional caution is required to avoid PIMs. Patients engaged in continuously using long-term medication should take precautions in daily life to alleviate related discomforts. Pharmacists should serve as a bridge between patients and physicians to enhance their health and improve their quality of life.

Phytochemical analysis and protective effects of Vaccinium macrocarpon (cranberry) in rats (Rattus norvegicus) following ethylene oxide-induced oxidative insult

ABSTRACT The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200–400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects.

Influence of aging on deterioration of patients with COVID-19.

Aging is an important factor affecting the deterioration of patients with coronavirus disease 2019 (COVID-19). The aging and degeneration of various tissues and organs in the elderly lead to impaired organ function. Underlying conditions such as chronic lung disease, cardiovascular disease, and diabetes in aged patients are associated with higher mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily interacts with the cell surface receptor angiotensin-converting enzyme (ACE) 2 and other accessory proteins such as 78 kDa glucose-regulated protein 78 (GRP78) and CD147. Thus, altered receptor signals in aging and chronic disease play a role in SARS-CoV-2 infection, and are associated with a higher risk of deterioration in different organs. In this review, after a brief introduction to the link between aging and receptors for SARS-CoV-2, we focus on the risk of deterioration in different organs of COVID-19 patients considering aging as the main factor. We further discuss the structural and/or physiological changes in the immune system and organs (lung, heart, kidney, vessels, nerve system), as well as those associated with diabetes, in aging patients, and speculate on the most likely mechanisms underlying the deterioration of COVID-19 patients.

Conditioning Regimens in Long-Term Pre-Clinical Studies to Support Development of Ex Vivo Gene Therapy: Review of Nonproliferative and Proliferative Changes.

Hematopoietic stem cell gene therapy has become a successful therapeutic strategy for some inherited genetic disorders. Pre-clinical toxicity studies performed to support the human clinical trials using viral-mediated gene transfer and autologous hematopoietic stem and progenitor cell (HSPC) transplantation are complex and the use of mouse models of human diseases makes interpretation of the results challenging. In addition, they rely on the use of conditioning agents that must induce enough myeloablation to allow engraftment of transduced and transplanted HSPC. Busulfan and total body irradiation (TBI) are the most commonly used conditioning regimens in the mouse. Lenticular degeneration and atrophy of reproductive organs are expected histopathological changes. Proliferative and nonproliferative lesions can be observed with different incidence and distribution across strains and mouse models of diseases. The occurrence of these lesions can interfere with the interpretation of pre-clinical toxicity and tumorigenicity studies performed to support the human clinical studies. As such, it is important to be aware of the background incidence of lesions induced by different conditioning regimens. We review the histopathology results from seven long-term studies, five using TBI and two using busulfan.

A CRITICAL APPRAISAL ON AGEING PROCESS IN AYURVEDA

Ayurveda being essentially the science of life and longevity narrates all aspects of life and puts special emphasis on Jara (ageing). The world population of the elderly is increasing and by the year 2030, older persons are projected to account for one in six people globally. Ageing is a process of unfavorable progressive changes associated with decline in vigor and ending in death. It is an irreversible and inevitable process and has multidimensional aspects. Everyone must undergo this phase of life at his/her own life. In Ayurveda, Jara (ageing) is clearly defined as that which has lost age means become old by the act of degeneration of bodily tissues and organs. It is described of two types- Kalaja jara and Akalaja jara. The Kalaja jara (timely ageing) can be regarded as chronological ageing where Dhatukshaya occurs whereas the Akalajajara (premature ageing) which occurs untimely i.e., before its prescribed time it can be regarded as biological ageing and is more intense than that of the chronological ageing. Several concepts are reported in Ayurveda regarding ageing process e.g, decade wise ageing process is described by Acharya Vagbhat and Sharangdhara. According to them one particular bodily feature is being degraded by each decade of lifespan, in the same way multiple theories are also analyzed in contemporary science. The whole biology of ageing has been dealt in present article within the Ayurvedic frame.

Gut bacteria-derived peptidoglycan induces a metabolic syndrome-like phenotype via NF-\u03baB-dependent insulin/PI3K signaling reduction in Drosophila renal system

Although microbiome–host interactions are usual at steady state, gut microbiota dysbiosis can unbalance the physiological and behavioral parameters of the host, mostly via yet not understood mechanisms. Using the Drosophila model, we investigated the consequences of a gut chronic dysbiosis on the host physiology. Our results show that adult flies chronically infected with the non-pathogenic Erwinia carotorova caotovora bacteria displayed organ degeneration resembling wasting-like phenotypes reminiscent of Metabolic Syndrome associated pathologies. Genetic manipulations demonstrate that a local reduction of insulin signaling consecutive to a peptidoglycan-dependent NF-κB activation in the excretory system of the flies is responsible for several of the observed phenotypes. This work establishes a functional crosstalk between bacteria-derived peptidoglycan and the immune NF-κB cascade that contributes to the onset of metabolic disorders by reducing insulin signal transduction. Giving the high degree of evolutionary conservation of the mechanisms and pathways involved, this study is likely to provide a helpful model to elucidate the contribution of altered intestinal microbiota in triggering human chronic kidney diseases.

Targeting senescent cells and tumor therapy (Review).

Cell senescence is caused by the activation of cell cycle inhibition pathways induced by an accumulation of cellular damage, where cells permanently leave the cell cycle. Senescent cells undergo changes in cell morphology, transcription, protein homeostasis, metabolism and other characteristic alterations. At the same time, senescent cells are able to resist apoptosis and accumulate in multiple organs and tissues in vivo. Senescent cells are capable of activating inflammatory factor secretion pathways, generating local, non-infectious inflammatory microenvironments within tissues, leading to organ degeneration and the development of aging-associated diseases. A large number of recently published studies have demonstrated that removing senescent cells from the body delays the occurrence of various aging-associated diseases. Therefore, the targeted killing of senescent cells potentially has important clinical applications in the treatment of various aging-associated diseases, aiming to improve the life span of patients. The present review summarizes recent progress that has been made in the field of senescent cell clearance and various anti-aging strategies. The history of cell senescence research is briefly reviewed, along with the association between cell senescence and tumor therapy. Furthermore, the potential of senescent cells to be used as therapeutic targets in various senescence-associated diseases is primarily discussed, and the limitations, as well as the future prospects of this line of research, are reviewed.

Transient pockets as mediators of gas molecules routes inside proteins: The case study of dioxygen pathway in homogentisate 1,2-dioxygenase and its implication in Alkaptonuria development

Alkaptonuria (AKU) is an ultra-rare disease caused by mutations in homogentisate 1,2-dioxygenase (HGD) enzyme, characterized by the loss of enzymatic activity and the accumulation of its substrate, homogentisic acid (HGA) in different tissues, leading to ochronosis and organ degeneration. Although the pathological effects of HGD mutations are largely studied, less is known about the structure of the enzyme, in particular the pathways for dioxygen diffusion to the active site, required for the enzymatic reaction, are still uninvestigated. In the present project, the combination of two in silico techniques, Molecular Dynamics (MD) simulation and Implicit Ligand Sampling (ILS), was used to delineate gas diffusion routes in HGD enzyme. A route from the central opening of the hexameric structure of the enzyme to the back of the active site trough the protein moiety was identified as the path for dioxygen diffusion, also overlapping with a transient pocket, which then assumes an important role in dioxygen diffusion. Along the route the sequence location of the missense variant E401Q, responsible for AKU development, was also found, suggesting such mutation to be conducive of enzymatic activity loss by altering the flow dynamics of dioxygen. Our in silico approach allowed also to delineate the route of HGA substrate to the active site, until now only supposed.

VEGF/CDK2 are involved in diabetic organ regeneration

Aim/hypothesisDiabetes is a hyperglycaemic disease treated by a set of allopathic drugs and natural biomolecules along with many variety of stem cell. We aim to investigate the role of these drugs in targeting common protein molecule in diabetes and its associated disease. We also aim to investigate the organ degeneration mechanistic pathway in diabetes. MethodWe have generated diabetes using streptozotocin injection and treated them using bone marrow transplantation and curcumin administration. The organs were studied histopathologically and by immunofluorescence analysis while drugs were studied Pharmacogenomically. ResultMice injected with streptozotocin have higher glucose and lower insulin, islet number/diameter, bone marrow cell number compared to control and bone marrow transplanted and curcumin administered mice. Histopathology staining demonstrates damaged morphology of pancreas, kidney, brain and cardiac muscle. Further, upon comparison of all allopathic and ayurvedic drugs used for diabetes several protein targets have been identified by reverse pharmacophore analysis using PharmMapper. VEGF, CDK2, insulin receptor, HSp90, eNOS, Fructose1,6 bisphosphatase, neprilysin, AchE, MAPK are several common protein targets of anti-diabetic drugs. ConclusionThis article demonstrates that VEGF and CDK2 are critical marker in organ damage in diabetes as well as organ regeneration.

Pathological Aspects of Haemonchosis in Goats and Sheeps

&lt;p class="awabstrak2"&gt;Haemonchosis in sheep and goats has a high prevalence rate in several regions in Indonesia and causes economic losses. The purpose of this paper is to explain the clinical symptoms and pathological aspects of &lt;em&gt;Haemonchus contortus&lt;/em&gt; infection so that knowledge is expected to help in controlling haemonchosis. Clinical symptoms of haemonchosis is characterised by decreased production, cachexia, and severe anaemia due to worms that sucking blood from the abomasal mucosa. In chronic infections the symptoms shows general oedema. Gross pathological findings are pale mucosa and carcass, hydrothorax, ascites, and haemorrhagic abomasum. Whereas histopathological features shows desquamation of villous abomasum, extensive hemorrhage of abomasal mucosa-submucosa, infiltration of large numbers of eosinophil and mononuclear cells, and cells undergoing degeneration and necrosis of internal organs. In general, the above exposure will show that haemonchosis usually associated with anaemia, cachexia, oedema, haemorrhage, infiltration of eosinophil and mononuclear cells in the abomasal mucosa.&lt;/p&gt;

A clinical case of Wilson — Konovalov disease in the practice of gastroenterologist

Wilson — Konovalov disease (in the English literature known as Wilson’s disease) is a rare inherited disease with autosomal recessive type of inheritance, which is based on a genetic defect in copper metabolism. Since copper is a part of almost all foods and plays a role of coenzyme in many processes in the body, this element cannot be excluded from the diet. For individuals with absence of excretion of copper ions from the cell, a violation of the fatty acid structure of the cell membrane is inevitable. As a result, its integrity is lost, which leads to degeneration of organs and tissues. Symptoms may include psychiatric (depression, apathy) and neurological disorders (gait disturbance, tremor, irritability), idiopathic hepatitis and cirrhosis, hemolytic anemia, disorders of the cardiovascular and musculoskeletal systems. The insidiousness of this disease is that copper can accumulate for years and not cause severe symptoms until it reaches a certain threshold level, and then in a very short time causes irreversible changes in the body. This threshold level is individual for everyone. It is clinically confirmed that the signs of liver damage are ahead of neurological manifestations by 10 years. Liver damage has been reported in all patients with neurological manifestations. Another important manifestation of the disease is the formation of the Kaiser‑Fleischer ring due to the accumulation of copper in the descemet’s membrane of the cornea. It is found in 95 % of people with neurological manifestations, but is practically not found in children with the disease. An important criterion for diagnosis is psychiatric and behavioural changes, which often precede hepatic manifestations, but are written off at puberty. Such a wide range of disorders is stipulated by the fact that copper is a cofactor of many enzymes in the body. Predictive testing and timely administration of specific treatment will help to avoid such processes. Untreated disease progresses with the development of acute liver failure with the subsequent need for liver transplantation.The authors give an overview of recent data on the etiology, pathogenesis, clinical manifestations, methods of treatment of Wilson — Konovalov disease, and present their own clinical observation of a complex case of Wilson — Konovalov disease in a young girl of 20 years old.

The tripartite interaction of phosphate, autophagy, and αKlotho in health maintenance.

Aging-related organ degeneration is driven by multiple factors including the cell maintenance mechanisms of autophagy, the cytoprotective protein αKlotho, and the lesser known effects of excess phosphate (Pi), or phosphotoxicity. To examine the interplay between Pi, autophagy, and αKlotho, we used the BK/BK mouse (homozygous for mutant Becn1F121A ) with increased autophagic flux, and αKlotho-hypomorphic mouse (kl/kl) with impaired urinary Pi excretion, low autophagy, and premature organ dysfunction. BK/BK mice live longer than WT littermates, and have heightened phosphaturia from downregulation of two key NaPi cotransporters in the kidney. The multi-organ failure in kl/kl mice was rescued in the double-mutant BK/BK;kl/kl mice exhibiting lower plasma Pi, improved weight gain, restored plasma and renal αKlotho levels, decreased pathology of multiple organs, and improved fertility compared to kl/kl mice. The beneficial effects of heightened autophagy from Becn1F121A was abolished by chronic high-Pi diet which also shortened life span in the BK/BK;kl/kl mice. Pi promoted beclin 1 binding to its negative regulator BCL2, which impairs autophagy flux. Pi downregulated αKlotho, which also independently impaired autophagy. In conclusion, Pi, αKlotho, and autophagy interact intricately to affect each other. Both autophagy and αKlotho antagonizes phosphotoxicity. In concert, this tripartite system jointly determines longevity and life span.

Evaluation of utricular and saccular function in BPPV patients: The role of VEMP in diagnosis

Aim: The pathological cause of Benign Paroxysmal Positional Vertigo (BPPV) is the degeneration of the otolith organs (utricle and sacculus). Vestibular Evoked Myogenic Potentials (VEMP) assess the functions of the otolith organs. The objective of this research was to evaluate the otolith organ functions of patients with unilateral idiopathic BPPV (canalolithiasis of the posterior and lateral semicircular canals) by cVEMP and oVEMP tests. Material and Methods: The study prospectively included 35 patients with BPPV (canalolithiasis of the posterior and lateral semicircular canals) and 30 healthy individuals. Bilateral cVEMP and oVEMP tests were administered to all participants. Participants were divided into three groups: control, BPPV-affected ear, and unaffected ear.Results: In our study, cVEMP and oVEMP abnormalities were statistically significantly different both between the affected and unaffected ear groups and between the affected ear and control groups. There were statistically significant differences in the cVEMP and oVEMP amplitude values both between the affected and unaffected ear groups and between the affected ear and control groups. Also, the asymmetry ratios of the cVEMP and oVEMP tests were statistically significantly different between the case group and the control group. The cVEMP and oVEMP wave latencies (p1, n1, p1-n1) were not statistically significantly different among the BPPV-affected ear, unaffected ear, and control groups. The results of measurements were not statistically significantly different between the posterior and lateral canal involvement subgroups of BPPV patients.Conclusion: Abnormal cVEMP and oVEMP test results, which are observed more frequently in patients with BPPV compared to the control group, indicate utricular and saccular degeneration. Higher oVEMP abnormality ratios compared to those of cVEMP in BPPV patients suggest that utricular dysfunction may be more common than saccular dysfunction.

Effects of Gambir leaves extract (Uncaria gambir Roxb.) in preventing the aging process inducted D-galactose on pancreas mice

Increasing level of reactive oxygen species (ROS) can damage the cell membrane and composition of DNA, leading to organ degeneration. Pancreas is among the organs that is sensitive to oxidative damage. Consumption of flavonoid-rich stuffs such as herbs, fruits and vegetables are believed to strengthen antioxidant capacity in the body in neutralizing free radicals. Gambir leaves have been used traditionally as remedies of various diseases. The most prominent active compounds in Gambir is flavonoid catechin which belongs to flavan-3-ols group. D-galactose is monosaccharide thatin high concentration can increase ROS generationand induce senescence in animal models. In this study, we aimed to observe the effect of Gambir leaves extract (GLE) in preventing ROS production and pancreas damage in galactose-induced mice model. Twenty-four female mice were divided into 4 groups amd injectedwith D-galactose 150 mg/kgBW intraperitoneally for 6 weeks. Three groups were supplemented with GLE 100; 200 and 400 mg/kgBW, respectively. Serum MDA, blood glucose and pancreas histopatology were analyzed. There is no significant difference among GLE-treated groups compared to control in the level of serum MDA (p=0,286), blood glucose fasting (p=0,051) and random (p=0,626), and pancreas histopathology: area of Langerhans islet (p=0,589) and perimeter of Langerhans islet (p=0,634). We did not found the histological damage in panreas. Interestingly, we found a trend increase in area, perimeter and cell number in Langerhans islet. Our data suggested a potential effect of GLE in increasing the growth of panreatic cells. Further study is necessary to elucidate the regenerative effect of GLE in damage pancreas such as streptozotocin-induced diabetes model.

Isolation, Identification and Pathogenicity of Flavobacterium columnare SGM4 in Catfish Clarias batrachus (Linnaeus 1758)

Objective: This study assessed the pathogenicity of Flavobacterium columnare isolated from the gill-rot of catfish, Clarias batrachus in West Bengal, India. Materials and Methods: The diseased catfish were examined as per standard laboratory practices. F. columnare SGM4 was identified based on the morphological, phenotypic and genotypic characterization. Abrasion-immersion and agar-disc diffusion methods were followed to assess the pathogenicity and antibiotic sensitivity of F. columnare, respectively. Results: The diseased catfish had white gills, tail rot, body discolouration, saddle-back, peeled skin, emaciation, and inflamed kidney. The yellow-pigmented rhizoid colonies from the gills of catfish were identified as F. columnare. Phylogenetically, F. columnare SGM4 branched with F. columnare strains. In abrasion-immersion challenge experiments, F. columnare SGM4 induced considerable mortalities (45%) in C. batrachus at 7.2×106 cells/mL at 24-30 °C. In challenged catfish, it caused cutaneous lesions, tail rot, white patches on the gills and degeneration of internal organs. F. columnare strains were highly sensitive to broad-spectrum antibiotics except for sulphafurazole. Conclusion: Adoption of good nursery practices and appropriate health management measures would help to minimize the development and spread of columnaris disease.

Heavy metals concentration and histopathological profile of some commercial fish species at Makoko Slum Neighbourhood Environment, Lagos, Nigeria

Potentially harmful substances such as pesticides, heavy metals, and hydro chemicals are often released into the aquatic environment. The objective of the present study was to assess the concentration of lead, copper, cadmium, chromium, and nickel in water samples from two different points (Mid-stream and downstream), also determine the levelsof Lead, Zinc, Manganese and copper in four commercially important fish species, Pseudotolithus senegalensis (croaker fish) and Ethmalosa fimbriata (bonga), Oreochromis mossambicus (Tilapia fish) and Bagrus bayad (silver catfish) from Makoko water body, Yaba, Lagos, Nigeria. Histopathological profile of the fish species selected was also examined. The results were compared to the World Health Organization (WHO) acceptable limit.The concentrations of the heavy metals were analyzed using Perkin Atomic Absorption Spectrophotometer (AAS). Pseudotholithus senegalensishad 3.01±0.02, 2.41±0.02, 3.48±0.01, 1.04±0.10 mg kg-1as the mean concentration of lead, zinc, manganese, and copper respectively, while E. fimbriatahad 1.06±0.02, 2.41±0.02, 4.14±0.01, 1.04±0.10 mg kg-1,O. mossambicushad 2.09±0.02, 3.11±0.04, 2.48±0.02, 0.62±0.01 mg kg-1and B. bayadhad 1.53±0.12, 3.61±0.05, 2.44±0.03, 0.66±0.01 mg kg-1 as the mean concentration of these metals in the tissues of these fishes. The concentrations of heavy metals were higher in the gills compared to other organs. The mean concentration of each heavy metal were varied significantly (p0.05) depending on the species of fish. In the histological analysis of the tissues, there was vacuolation of hepatocytes, inflammation, and necrosis. In the muscle, there was a mild lesion, necrosis, inflammation, and cellular degenerations. But the level of tissue and organ degeneration is more severe in the gills. The study showed that some levels of these metals were within the permissible recommended allowed limit for human consumption. It is concluded that Makoko Lagoon water body and fishes are heavily contaminated with heavy metals.

Спектр і частота мутацій гена ATP7B в різних популяціях та етнічних групах

Wilson disease (WD) – autosomal recesive disorder for which effective inexpensive therapy has been developed. Such success was achieved through a detailed study of the structure of the protein, and the establishment of the correspondence between the individual Copper-binding ATPase domains, and the primary sequence of the gene encoding it. These studies gave an idea of the functioning and role of metal transport of each individual protein domain, and helped find ways to correct the pathology. Since copper is a part of almost all foods, and is coenzyme in many processes in the body, it is not possible to exclude this element from the diet. For people with a lack of excretion of copper ions from a cell inevitably there is a violation of the structure of the fatty acids of the cell membrane. Because of this, its integrity is lost, and as a result, degeneration of organs and tissues. Avoid such processes will help predictive testing, but the timely appointment of specific treatment. Diagnosis of this disease is complicated not only by non-specific manifestations, but by a wide range of mutations. Almost 300 mutations in ATP7B gene that are associated with WD development have been described. Although most WD-causing mutations are rare and only reported in single families, some are more common and account for a large portion of WD cases. Therefore, genetic testing of mutations will become possible only when the list of the most frequent for our population is formed, and an algorithm of medical genetic counseling of persons at high risk of development of the disease of Wilson-Konovalov is compiled. In Ukraine, such a study has not been conducted so there is no information about the frequency and range of mutations in this gene for our population. The majority of known mutations affecting this gene are frequent in different populations. It is important to diagnose Wilson disease as early as possible, since severe liver damage can occur before there are any signs of the disease. Thus, the purpose of my work is to conduct a study on the distribution of the frequency of mutations in the ATP7B gene on the basis of literature data in five neighboring countries: Poland, Austria, Latvia, Germany and Western Russia, in order to form the list of the most likely mutations in our population to improve WD diagnosis. The results obtained during the analysis of literary data showed that the most common cause of the disease among residents of Europe and western Russia is the mutation H1069Q. But the literature describes many other specific mutations to each individual population. Thus, it is expected that besides the major mutation of H1069Q, our population will have its own specific mutations. It is advisable to start a genetic study the mutation H1069Q and further sequencing of the exon 8 in person with WD.

Mesenchymal stem cells and their mitochondrial transfer: a double-edged sword

Mitochondrial dysfunction has been linked to many diseases including organ degeneration and cancer. Mesenchymal stem cells/stromal cells (MSCs) provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for tissue regeneration. Increasing evidence suggests that MSCs can directly donate mitochondria to recover from cell injury and rescue mitochondrial damage-provoked tissue degeneration. Meanwhile, cancer cells and cancer stromal cells also cross-talk through mitochondrial exchange to regulate cancer metastasis. This review summarizes the research on MSCs and their mitochondrial transfer. It provides an overview of the biology, function, niches and signaling that play a role in tissue repair. It also highlights the pathologies of cancer growth and metastasis linked to mitochondrial exchange between cancer cells and surrounding stromal cells. It becomes evident that the function of MSC mitochondrial transfer is a double-edged sword. MSC mitochondrial transfer may be a pharmaceutical target for tissue repair and cancer therapy.

Stabilization of amyloidogenic immunoglobulin light chains by small molecules

In Ig light-chain (LC) amyloidosis (AL), the unique antibody LC protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. As a step toward developing treatments for AL patients with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, we introduce small-molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which can slow or stop the amyloidogenicity cascade at its origin. A protease-coupled fluorescence polarization-based high-throughput screen was employed to identify small molecules that kinetically stabilize LCs. NMR and X-ray crystallographic data demonstrate that at least one structural family of hits bind at the LC-LC dimerization interface within full-length LCs, utilizing variable-domain residues that are highly conserved in most AL patients. Stopping the amyloidogenesis cascade at the beginning is a proven strategy to ameliorate postmitotic tissue degeneration.

Cell-type-specific role of lamin-B1 in thymus development and its inflammation-driven reduction in thymus aging.

Cellular architectural proteins often participate in organ development and maintenance. Although functional decay of some of these proteins during aging is known, the cell‐type‐specific developmental role and the cause and consequence of their subsequent decay remain to be established especially in mammals. By studying lamins, the nuclear structural proteins, we demonstrate that lamin‐B1 functions specifically in the thymic epithelial cells (TECs) for proper thymus organogenesis. An up‐regulation of proinflammatory cytokines in the intra‐thymic myeloid immune cells during aging accompanies a gradual reduction of lamin‐B1 in adult TECs. We show that these cytokines can cause senescence and lamin‐B1 reduction of the young adult TECs. Lamin‐B1 supports the expression of TEC genes that can help maintain the adult TEC subtypes we identified by single‐cell RNA‐sequencing, thymic architecture, and function. Thus, structural proteins involved in organ building and maintenance can undergo inflammation‐driven decay which can in turn contribute to age‐associated organ degeneration.