Molecular medicine reports最新文献

Pelvic organ prolapse (POP) is a prevalent condition among middle‑aged and older women, and is associated with the irregular production and breakdown of the extracellular matrix. Mechanical forces serve a key role in preserving the equilibrium between matrix synthesis and degradation, thereby supporting the structural integrity of pelvic floor tissues. The aim of the present study was to investigate alterations in the composition of vaginal wall tissues in individuals suffering from POP and to investigate the molecular mechanisms through which mechanical forces trigger fibroblast apoptosis and influence collagen expression via the integrin‑β1/TGF‑β1 signaling pathway. Masson's trichrome and Elastica van Gieson staining were used to examine the pathological alterations in the tissue associated with POP. Analysis of immunofluorescence, western blotting and reverse transcription‑quantitative PCR data was performed to assess changes in the levels of proteins and genes such as collagen, integrin‑β1, TGF‑β1, MMP‑1 and tissue inhibitor of metalloproteinase‑1 (TIMP‑1). Fibroblasts were incubated with an integrin‑β1 antagonist RGD peptide to mimic cellular injury induced by mechanical forces, and cell migration and apoptosis were analyzed using scratch assays and flow cytometry. Cytoskeletal alterations were detected via immunofluorescence staining, and western blot analysis was conducted to examine the expression levels of integrin‑β1, TGF‑β1, TIMP‑1, MMP‑1, collagen type I α1 chain (COL1A1) and collagen type III α1 chain (COL3A1) across various groups. Analysis revealed that in the POP group, the collagen fibers in the vaginal wall tissues were loose and irregularly arranged, the number of elastic fibers was reduced and the structure was degraded. Furthermore, stress fibers were incomplete and their functions were impaired, resulting in damage to the connective tissue structure of the pelvic floor. Integrin‑β1 was key for fibroblast migration, apoptosis and collagen synthesis. Additionally, the integrin‑β1/TGF‑β1 signaling pathway served a role in mediating fibroblast apoptosis, and influencing the synthesis and metabolism of COL1A1 and COL3A1 induced by mechanical forces. Understanding the underlying pathogenesis of pelvic floor organ prolapse could pave the way for future investigations into innovative prevention and treatment strategies.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical data shown in Fig. 1C on p. 5 were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been published in the journal Archives of Biochemistry and Biophysics prior to the submission of this paper to Molecular Medicine Reports. In view of the fact that the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 24: 833, 2021; DOI: 10.3892/mmr.2021.12473].

Asthma is a chronic allergic respiratory disease lacking effective therapies. The present study investigated the anti‑asthmatic properties of lipid mediators using an ovalbumin (OVA)‑induced allergic asthma model. Lipid mediators (LM; 17S‑monohydroxy docosahexaenoic acid, resolvin D5 and protectin DX at a ratio of 3:47:50) were derived from docosahexaenoic acid through soybean lipoxygenase. LM treatment significantly alleviated major features of allergic asthma, including inflammatory cell infiltration, with a particular reduction in eosinophils in bronchoalveolar lavage fluid, downregulation of Th2 cytokine expression, attenuation of airway remodeling, and oxidative stress, thereby closely resembling the normal condition. Additionally, a significant increase in the serum levels of interleukin‑6 [167.12±6.25 pg/ml; P<0.0001 vs. negative control (NC) group], tumor necrosis factor‑α (109.17±7.17 pg/ml; P<0.0001 vs. NC group) and IgE (90.24±5.98 ng/ml; P<0.0001 vs. NC group) was observed following OVA challenge; however, oral administration of LM resulted in a notable reduction in these levels to 99.45±6.12 pg/ml (P<0.001 vs. OVA group), 62.51±4.03 pg/ml (P<0.001 vs. OVA group) and 56.50±2.70 ng/ml (P<0.001 vs. OVA group), respectively. Furthermore, the heightened expression of Th2‑related cytokines induced by OVA was observed to be restored closely to normal conditions following LM treatment, as demonstrated for both gene and protein expression levels. Histological analysis demonstrated that LM mitigated inflammatory cell infiltration while reducing mucus secretion. Additionally, LM effectively ameliorated oxidative stress in OVA‑induced asthma, with a significant increase in the activity of superoxide dismutase (~185% vs. OVA group; P<0.001), elevated levels of glutathione (~74% higher than the OVA group; P<0.001) and reduced content of malondialdehyde (~40% lower than the OVA group; P<0.001) in lung tissues. Collectively, these findings suggested that LM effectively protected lung tissues from inflammation and oxidative stress, thereby representing a promising therapeutic option for the treatment of allergic asthma.

β‑sitosterol (SIT) has anti‑inflammatory, anti‑tumor and anti‑fibrotic effects. However, the precise mechanisms underlying its efficacy in keloid treatment remain elusive. The present study aimed to elucidate the therapeutic effect of SIT on keloids. The active components of Fructus arctii, target molecules of these components and disease‑associated target molecules were identified and retrieved from various databases. Molecular docking was employed to evaluate the binding affinity of the active compounds for key targets. Cell viability and proliferation were evaluated via CCK‑8 and EdU assays, while cell migration capacity was assessed via wound healing assays and cell migration and invasion abilities were determined via Transwell assays. A rescue study involving YS‑49 was conducted. Western blot analysis was performed to assess the expression levels of proteins associated with EMT and proteins involved in the PI3K/AKT signaling pathway. A subcutaneous keloid fibroproliferative model was established in nude mice and immunohistochemical staining was performed on tissue sections. By intersecting the keloid targets, 29 targets were identified, with 10 core targets revealed by protein-protein interaction analysis. Molecular docking revealed a robust binding affinity between SIT and PTEN. In addition to inhibiting cell viability, invasion and migration, SIT significantly decreased the levels of phosphorylated (p‑)PI3K and p‑AKT, downregulated the protein expression of Vimentin and Snail proteins and increased the protein expression of Zonula Occludens‑1 and E‑cadherin. YS‑49 reversed the inhibitory effect of SIT on keloid in SIT‑treated cells. In vivo experiments demonstrated that SIT suppressed the growth of a keloid model in nude mice and increased PTEN expression. The present study provided the first evidence that SIT inhibits keloid proliferation, migration and invasion by modulating the PTEN/PI3K/AKT signaling pathway, suggesting its potential as a novel therapeutic approach for keloid treatment.

With the high production and use of plastic products, a large amount of microplastics (MPs) is generated by degradation, which causes environmental pollution. MPs are particles with a diameter <5 mm; further degradation of MPs produces nano‑plastics (NPs), which could further increase the damage to cells when entering the human body. Therefore, the present review summarizes the effect of MP and NP deposition on the human gastrointestinal tract and the underlying injury mechanism of oxidative stress, inflammation and apoptosis, as well as the potential mechanism of glucose and liver lipid metabolism disorder. The present review provides a theoretical basis for research on the mechanisms of MPs in gastrointestinal injury and liver metabolism disorder. Further studies are needed for prevention and treatment of gastrointestinal diseases caused by MPs and NPs.

Flavonoids are a group of polyphenolic compounds distributed in vegetables, fruits and other plants, which have considerable antioxidant, anti‑tumor and anti‑inflammatory activities. Several types of gastrointestinal (GI) cancer are the most common malignant tumors in the world. A large number of studies have shown that flavonoids have inhibitory effects on cancer, and they are recognized as a class of potential anti‑tumor drugs. Therefore, the present review investigated the molecular mechanisms of flavonoids in the treatment of different types of GI cancer and summarized the drug delivery systems commonly used to improve their bioavailability. First, the classification of flavonoids and the therapeutic effects of various flavonoids on human diseases were briefly introduced. Then, to clarify the mechanism of action of flavonoids on different types of GI cancer in the human body, the metabolic process of flavonoids in the human body and the associated signaling pathways causing five common types of GI cancer were discussed, as well as the corresponding therapeutic targets of flavonoids. Finally, in clinical settings, flavonoids have poor water solubility, low permeability and inferior stability, which lead to low absorption efficiency in vivo. Therefore, the three most widely used drug delivery systems were summarized. Suggestions for improving the bioavailability of flavonoids and the focus of the next stage of research were also put forward.

Cigarette smoke (CS) is a key contributor of chronic obstructive pulmonary disease (COPD); however, its role in the pathogenesis of COPD has not been fully elucidated. N‑acetyl‑L‑cysteine (NAC), as an antioxidant, has been used in the treatment of COPD; however, the mechanisms of action of NAC are not fully understood. Alveolar epithelial type 2 (ATII) cells serve an essential role in the maintenance of alveolar integrity. The aim of the present study was to identify the effect of CS on rat lungs and ATII cells. A subacute lung injury model of Wistar rats was established using CS exposure for 4 weeks. Interalveolar septa widening, infiltration of inflammatory cells, edema fluid in airspaces and abnormal enlargement of airspaces were observed through H&E staining. ELISA revealed that NAC could protect against CS‑induced increases in serum levels of malondialdehyde and decreases in serum levels of superoxide dismutase. Additionally, 8‑hydroxy‑deoxyguanosine was detected using immunohistochemical staining, and this was also expressed at increased levels in the lung tissue of the CS‑exposed group. In addition, the expression levels of Bcl‑2, BAX and caspase‑3 p12 in lung tissue were detected by western blotting or immunohistochemical staining. The expression levels of Bcl‑2 decreased and those of caspase3 p12 were increased in response to CS exposure when compared with those in the control group. These effects were prevented by treatment with NAC. In vitro, the effect of CS extract (CSE) on rat lung epithelial‑6‑T‑antigen negative (RLE‑6TN) cells was observed, flow cytometry was used to detect intracellular reactive oxygen species (ROS) levels and the occurrence of apoptosis, and the content of glutathione (GSH) was detected using a colorimetric assay. Additionally, the expression levels of heme oxygenase‑1 (HO‑1), p53 and Bcl‑2 were examined by western blotting, and HO‑1 mRNA expression was also examined using reverse transcription‑quantitative PCR. The results of the present study revealed that CSE induced apoptosis of RLE‑6TN cells, accompanied by increased levels of intracellular ROS and exhaustion of GSH. Significantly increased protein levels of HO‑1 and p53, as well as decreased protein levels of Bcl‑2 were also observed. These effects were prevented by administration of NAC. Overall, these findings suggested that CS could promote apoptosis in rat lung tissues and alveolar epithelial cells by inducing intracellular oxidative injury, and NAC may serve an antioxidant role by replenishing the intracellular GSH content.

Acetaminophen (APAP) is safe at therapeutic doses; however, when ingested in excess, it accumulates in the liver and leads to severe hepatotoxicity, which in turn may trigger acute liver failure (ALF). This is known as APAP poisoning and is a major type of drug‑related liver injury. In the United States, APAP poisoning accounts for ≥50% of the total number of ALF cases, making it one of the most common triggers of ALF. According to the American Association for the Study of Liver Diseases, the incidence of APAP‑associated hepatotoxicity has increased over the past few decades; however, the mechanism underlying liver injury due to APAP poisoning has remained inconclusive. The present study aims to comprehensively review and summarize the latest research progress on the mechanism of APAP‑induced liver injury, and to provide scientific and effective guidance for the clinical treatment of APAP poisoning through in‑depth analysis of the metabolic pathways, toxicity‑producing mechanisms and possible protective mechanisms of APAP in the liver.

Low back pain (LBP) is a leading cause of disability worldwide. Although not all patients with Modic changes (MCs) experience LBP, MC is often closely associated with LBP and disc degeneration. In clinical practice, the focus is usually on symptoms related to MC, which are hypothesized to be associated with LBP; however, the link between MC and nerve compression remains unclear. In cases of intervertebral disc herniation, nerve compression is often the definitive cause of symptoms. Recent advances have shed light on the pathophysiology of MC, partially elucidating its underlying mechanisms. The pathogenesis of MC involves complex bone marrow‑disc interactions, resulting in bone marrow inflammation and edema. Over time, hematopoietic cells are gradually replaced by adipocytes, ultimately resulting in localized bone marrow sclerosis. This process creates a barrier between the intervertebral disc and the bone marrow, thereby enhancing the stability of the vertebral body. The latest understanding of the pathophysiology of MC suggests that chronic inflammation plays a significant role in its development and hypothesizes that the complement system may contribute to its pathological progression. However, this hypothesis requires further research to be confirmed. The present review we proposed a pathological model based on current research, encompassing the transition from Modic type 1 changes (MC1) to Modic type 2 changes (MC2). It discussed key cellular functions and their alterations in the pathogenesis of MC and outlined potential future research directions to further elucidate its mechanisms. Additionally, it reviewed the current clinical staging and pathogenesis of MC, recommended the development of an updated staging system and explored the prospects of integrating emerging artificial intelligence technologies.

Following the publication of this article, an interested reader drew to the Editor's attention that a pair of data panels in the cellular images shown in Fig. 1A on p. 2317 appeared to be overlapping, such that data which were intended to show the results from differently performed experiments had appparently been derived from the same original source. Moreover, in Fig. 1C and 5A, there appeared to be discrete splicing events for gel slices featured in these figure parts, and for the immunoblotting experiments shown in Fig. 2B, striking likenesses of certain of the bands appeared in different positions in different gels relative to each other where different experimental conditions were being shown, which seemed difficult to attribute purely to coincidence. After having conducted an internal investigation, the Editor of Molecular Medicine Reports agrees with the reader that there were anomalies associated with the presentation of Figs. 1, 2 and 5. Therefore, on the grounds of a lack of confidence in the presented data, the Editor has decided that the article should be retracted from the publication. Upon contacting the authors, all the authors agreed with the decision to retract this paper, except for Dr Randal Johnston, who was not contactable owing to his retirement several years ago. The Editor apologizes to the readership for any inconvenience caused, and we also thank the reader for bringing this matter to our attention. [Molecular Medicine Reports 11: 2315‑2321, 2015; DOI: 10.3892/mmr.2014.2949].