Enhancing osteoporosis treatment with engineered mesenchymal stem cell-derived extracellular vesicles: mechanisms and advances

Abstract As societal aging intensifies, the incidence of osteoporosis (OP) continually rises. OP is a skeletal disorder characterized by reduced bone mass, deteriorated bone tissue microstructure, and consequently increased bone fragility and fracture susceptibility, typically evaluated using bone mineral density (BMD) and T-score. Not only does OP diminish patients’ quality of life, but it also imposes a substantial economic burden on society. Conventional pharmacological treatments yield limited efficacy and severe adverse reactions. In contemporary academic discourse, mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) have surfaced as auspicious novel therapeutic modalities for OP. EVs can convey information through the cargo they carry and have been demonstrated to be a crucial medium for intercellular communication, playing a significant role in maintaining the homeostasis of the bone microenvironment. Furthermore, various research findings provide evidence that engineered strategies can enhance the therapeutic effects of EVs in OP treatment. While numerous reviews have explored the progress and potential of EVs in treating degenerative bone diseases, research on using EVs to address OP remains in the early stages of basic experimentation. This paper reviews advancements in utilizing MSCs and their derived EVs for OP treatment. It systematically examines the most extensively researched MSC-derived EVs for treating OP, delving not only into the molecular mechanisms of EV-based OP therapy but also conducting a comparative analysis of the strengths and limitations of EVs sourced from various cell origins. Additionally, the paper emphasizes the technical and engineering strategies necessary for leveraging EVs in OP treatment, offering insights and recommendations for future research endeavors

Bleeding due to successive duodenal and rectal ulcers in an 81-year-old patient with severe COVID-19: a case report

Abstract Background In the early stages of the coronavirus disease 2019 (COVID-19) outbreak, the most widely recognised symptoms of the disease were fever, cough, shortness of breath, myalgia, and fatigue. However, in addition to these symptoms, COVID-19 can cause systemic symptoms outside the lungs. Older patients with severe COVID-19 often require admission to the intensive care unit (ICU). Acute rectal ulcer bleeding, characterised by painless, profuse haematochezia, caused by solitary or multiple rectal ulcers, is one of the main causes of severe haematochezia in patients with COVID-19 in the ICU. However, recurrent duodenal ulcer bleeding followed by rectal ulcer bleeding has not previously been reported in older patients during ICU treatment for severe COVID-19. Cases presentation Herein, we report the case of an 81-year-old woman admitted to the emergency department due to severe COVID-19 and transferred to the ICU 2 days later for treatment. During treatment in the ICU, the patient developed recurrent duodenal ulcer bleeding and underwent endoscopic electrocoagulation haemostasis and gastroduodenal artery embolisation. However, the night after the final haemostatic operation, due to rectal ulcer bleeding, the patient discharged bloody stools intermittently, which was effectively controlled using endoscopic electrocoagulation, topical medication, blood transfusion, and haemostatic drugs. Conclusions To the best of our knowledge, this is the first report of duodenal ulcer bleeding followed by rectal ulcer bleeding in an older patient with severe COVID-19 infection. This report creates awareness for clinicians about the multiple and complex gastrointestinal symptoms that may occur during COVID-19 treatment

Methylglyoxal Induces Systemic Symptoms of Irritable Bowel Syndrome

<div><p>Patients with irritable bowel syndrome (IBS) show a wide range of symptoms including diarrhea, abdominal pain, changes in bowel habits, nausea, vomiting, headache, anxiety, depression and cognitive impairment. Methylglyoxal has been proved to be a potential toxic metabolite produced by intestinal bacteria. The present study was aimed at investigating the correlation between methylglyoxal and irritable bowel syndrome. Rats were treated with an enema infusion of methylglyoxal. Fecal water content, visceral sensitivity, behavioral tests and serum 5-hydroxytryptamine (5-HT) were assessed after methylglyoxal exposure. Our data showed that fecal water content was significantly higher than controls after methylglyoxal exposure except that of 30 mM group. Threshold volumes on balloon distension decreased in the treatment groups. All exposed rats showed obvious head scratching and grooming behavior and a decrease in sucrose preference. The serum 5-HT values were increased in 30, 60, 90 mM groups and decreased in 150 mM group. Our findings suggested that methylglyoxal could induce diarrhea, visceral hypersensitivity, headache as well as depression-like behaviors in rats, and might be the key role in triggering systemic symptoms of IBS.</p></div

Effects of methylglyoxal on serum 5-HT level.

<p>The serum 5-HT levels of 30 mM, 60 mM and 90 mM groups were markedly higher than controls. The difference between 120 mM group and controls was not significantly. The level of 5-HT in 150 mM group rats was decreased than controls. **<i>p</i><0.01 versus controls, *<i>p</i><0.05 versus controls.</p

Effects of methylglyoxal on head scratching and grooming behaviors.

<p>The time of scratching behavior in all treatment groups markedly increased compared with controls. **<i>p</i><0.01 versus controls.</p

Effects of methylglyoxal on sucrose preference test.

<p>The SPT scores of the 150 mM group were decreased. *<i>p</i><0.05 versus controls.</p