It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the ...mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC-Exos) in wound skin tissue repair. Flow cytometry and electron microscopy were carried out to identify ADSCs and ADSC-Exos, respectively; RT-qPCR was performed to assess the lncRNA H19 (H19), microRNA19b (miR-19b) and SRY-related high-mobility-group box 9 (SOX9) levels; Western blotting was carried out to evaluate collagen and β-catenin expression; CCK-8, scratch and transwell assays were conducted to evaluate human skin fibroblast (HSF) cell proliferation, migration and invasion, respectively; the potential binding sites between H19 and miR-19b, miR-19b and SOX9 were detected by dual-luciferase reporter gene assay and RIP assay; and H&E staining was conducted to observe skin wound tissues. ADSC-Exos accelerated the proliferation, migration and invasion of HSF cells via H19. H19 acts as a molecular sponge towards miR-19b, which targets SOX9. ADSC-Exos inhibited miR-19b expression via H19, resulting in accelerated HSF proliferation, migration and invasion. ADSC-Exos upregulated SOX9 to activate the Wnt/β-catenin pathway, resulting in accelerated HSF cell proliferation, migration and invasion, and ADSC-Exos promoted skin wound healing via H19 in mice.
The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.
This study reveals that the long non-coding RNA H19 is highly expressed in exosomes derived from adipose mesenchymal stem cells and accelerates the proliferation, migration and invasion of human skin fibroblasts by upregulation of SOX9 and activation of the Wnt/β-catenin pathway The authors show that H19 affects SOX9 expression via the microRNA miR-19b to promote wound healing in injured skin.
Angiogenesis plays a key in the process of tissue repair and wound healing. Human adipose-derived mesenchymal stem cells (HADSCs) have been found to act a promotion role during angiogenesis. ...Moreover, miR-125a-3p in HADSCs could promote the angiogenesis of HUVECs, but their specific mechanism in wound healing needs further study. Western blotting and qRT-PCR were used for detecting the protein and mRNA level, respectively. Exosomes were isolated successfully, and transmission electron microscope was used to identify exosomes. Angiogenesis, cell migration, and proliferation were detected with tube formation, wound healing, and MTT assays. The interactions of miR-125a-3p and PTEN were validated using dual-luciferase reporter assay. Animal model was used to evaluate the effect of miR-125a-3p on wound healing. HADSCs-exosome remarkably promoted the viability, migration, and angiogenesis of HUVECs. Knockdown of miR-125a-3p in HADSCs could inhibit the effect of HADSCs–exosome, while overexpression of miR-125a-3p could further promote the effect of HADSCs–exosome on HUVECs. MiR-125a-3p from HADSCs–exosome inhibited the expression of PTEN in HUVECs. Knockdown of PTEN promoted the viability, migration, and angiogenesis of HUVECs and reversed the effect of miR-125a-3p knockdown on HUVECs. Finally, miR-125a-3p from HADSCs–exosome could promote wound healing and angiogenesis in mice by inhibiting PTEN in mice wound granulation tissues. MiR-125a-3p from the HADSCs–exosome promoted the wound healing and angiogenesis, and these effects were achieved through regulating PTEN. This study may provide a new thought for the treatment and prevention of tissue repair.
Peutz–Jeghers syndrome is a rare autosomal dominant inherited disorder characterized by mucocutaneous pigmentation and hamartomatous gastrointestinal polyposis. A growing body of evidence has shown ...that Peutz–Jeghers syndrome could cause an increased risk of various cancers, yet the range of cancer risk estimates was wide among different studies. In this retrospective cohort study, 336 patients with Peutz–Jeghers syndrome in China were enrolled. The clinical characteristics, cancer spectrum, relative cancer risks, and cumulative cancer risks were analyzed. In total, 52 patients were diagnosed of cancer in the follow-up period, at a median age of 41 years (range: 21–67). The relative risk for cancer in Peutz–Jeghers syndrome patients was 63.858 (confidence interval: 47.514–85.823), and the cumulative cancer risk at the age of 60 years was 55%. Colorectal cancer was the most common cancer for Peutz–Jeghers syndrome patients (relative risk: 237.918, confidence interval: 154.417–366.572) and the cumulative cancer risk at the age of 60 years was 28%. There was a statistically significant difference in the cumulative cancer risk between patients with family history and those without family history, as well as between patients living in rural area and those living in urban areas (p < 0.05), while no significant effects of gender and intussusception history on the cumulative cancer risk was found (p > 0.05). Hopefully, our study may contribute to the management of this rare disorder and establishment of related surveillance projects, especially in China.
Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas. This study aimed to compare the natural course of alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis ...(ICP).
CP patients admitted to our center from January 2000 to December 2013 were enrolled. Characteristics were compared between ACP and ICP patients. Cumulative rates of diabetes mellitus (DM), steatorrhea, pancreatic stone, pancreatic pseudocyst, biliary stricture, and pancreatic cancer after the onset and the diagnosis of CP were calculated, respectively. The cumulative rates of DM and steatorrhea after diagnosis of pancreatic stone were also calculated.
A total of 2,037 patients were enrolled. Among them, 19.8% (404/2,037) were ACP and 80.2% (1,633/2,037) were ICP patients. ACP and ICP differs in many aspects, especially in gender, age, smoking, complications, morphology of pancreatic duct, and type of pain. The development of DM, steatorrhea, PPC, pancreatic stone, and biliary stricture were significantly earlier and more common in ACP patients. No significant difference was observed for pancreatic cancer development. There was a rather close correlation between exocrine/endocrine insufficiency and pancreatic stone in ACP patients, which was much less correlated in ICP patients.
The long-term profile of ACP and ICP differs in some important aspects. ACP patients usually have a more severe course of CP. These differences should be recognized in the diagnosis and treatment of CP.
Risk of pancreatic cancer may increase in chronic pancreatitis patients.
This study aimed to identify the incidence of and risk factors for pancreatic cancer in chronic pancreatitis patients.
Chronic ...pancreatitis patients admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic cancer and survival rates were calculated. The standardized incidence ratio was calculated based on the pancreatic cancer incidence in general population of China. Risk factors for pancreatic cancer were identified.
In a total of 1656 patients, the median follow-up duration was 8.0 years. Pancreatic cancer was detected in 21 patients (1.3%). The expected number of cases of pancreatic cancer was 1.039, yielding a standardized incidence ratio of 20.22. The standardized incidence ratios for patients with a >60 pack-year smoking history were much higher (145.82). Two risk factors for pancreatic cancer were identified: age at the onset of chronic pancreatitis (hazard ratio, 1.05) and a >60 pack-year smoking history (hazard ratio, 11.83).
The risk of pancreatic cancer is markedly increased in chronic pancreatitis patients compared with the general population, especially in patients with an older age at onset and a >60 pack-year smoking history. The high-risk populations were suggested to be followed up closely.
The morphology of donor‐acceptor heterojunction interface significantly affects the electron/hole processes in organic solar cells, including charge transfer (CT), exciton dissociation (ED), and ...charge recombination (CR). Here, to investigate interface molecular configuration effects, the donor‐acceptor complexes with face‐on, edge‐on, and end‐on configurations were constructed as model systems for the p‐SIDT(FBTTh2)2/C60 heterojunction. The geometries, electronic structures, and excitation properties of monomers and the complexes with three configurations were studied based on density functional theory (DFT) and time‐dependent DFT calculations with optimally tuned range separation parameters and solid polarization effects. In terms of Marcus theory, the rate constants of ED and CR processes were analyzed. The results show that most of the excited states for p‐SIDT(FBTTh2)2 exhibit an intramolecular CT character, and the similarity of the excitation characters (CT and local excitation) and energies among three complexes with different configurations indicate that the electronic structure and excitation properties are insensitive to the interfacial molecular configurations. However, the rates of ED and CR processes heavily depend on it. These results underline the importance of controlling molecular configuration and then the morphology at the heterojunction interface in organic solar cells.
Based on density functional theory (DFT) and time‐dependent DFT calculations with optimally tuned range separation parameters and solid polarization effects, the exciton dissociation and charge recombination rates of p‐SIDT(FBTTh2)2/C60 complexes calculated using Marcus theory show that they strongly depend on the molecular configurations in an organic heterojunction interface.
To report Peutz-Jeghers syndrome (PJS) cases with non-definitive clues in the family or personal history and finally diagnosed through pathological examination and STK11 gene mutation test. Early ...diagnosis of PJS is important and may be based on a family history with selective features among family members, and the pathological information is the key. The novel mutations also expand the STK11 variant spectrum.
Background and Aim
Pancreatic extracorporeal shock wave lithotripsy (P‐ESWL) is a first‐line treatment for chronic pancreatitis (CP) patients with pancreatic stones. However, the performance of ...P‐EWSL in geriatric patients remains unclear. We aimed to evaluate the safety and efficacy of P‐ESWL for them.
Methods
This prospective study was conducted in painful CP patients who underwent P‐ESWL. Patients aged over 65 years were included in geriatric group; patients aged under 65 years were assigned to control group. For the long‐term follow‐up investigation, geriatric patients were matched with patients from the control group in a 1:1 ratio. Primary outcomes were complications of P‐ESWL and pain relief. Secondary outcomes included stone clearance, physical and mental health, quality of life score, changes in exocrine and endocrine pancreatic function, and survival.
Results
From March 2011 to March 2016, P‐ESWL was performed in 1404 patients (72 in the geriatric group and 1332 in the control group). No significant differences were observed in complications of P‐ESWL between the two groups (P = 0.364). Among the 67 (67/72, 93.1%) geriatric patients who underwent follow up for 4.02 years, complete pain relief was achieved in 53 patients, which was not significantly different from that of matched controls (54/70; P = 0.920). The death in the geriatrics was significantly higher (P = 0.007), but none of them were correlated with P‐ESWL.
Conclusions
P‐ESWL is safe and effective for geriatric CP patients with pancreatic stones. It can promote significant pain relief and stone clearance and improve quality of life and mental and physical health.
Currently, for ovarian cancer, which has the highest mortality rate among all gynecological cancers, the standard treatment protocol is initial tumor cytoreductive surgery followed by platinum-based ...combination chemotherapy. Although the survival rate after standard treatment has improved, the therapeutic effect of traditional chemotherapy is very limited due to problems such as resistance to platinum-based drugs and recurrence. With the advent of the precision medicine era, molecular targeted therapy has gradually entered clinicians' view, and individualized precision therapy has been realized, surpassing the limitations of traditional therapy. The detection of genetic mutations affecting treatment, especially breast cancer susceptibility gene (BRCA) mutations and mutations of other homologous recombination repair defect (HRD) genes, can guide the targeted drug treatment of patients, effectively improve the treatment effect and achieve a better patient prognosis. This article reviews different sites and pathways of targeted therapy, including angiogenesis, cell cycle and DNA repair, and immune and metabolic pathways, and the latest research progress from preclinical and clinical trials related to ovarian cancer therapy.
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