International journal of molecular medicine最新文献

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the histological data shown in Fig. 7E were strikingly similar to data appearing in different form in an article written by different authors at different research institutes that had already been published in the journal International Journal of Molecular Sciences. In view of the fact that the abovementioned data had already apparently been published prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 1149‑1156, 2019; DOI: 10.3892/ijmm.2018.4044].

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial and/or venous thrombosis, pathological pregnancies and persistent antiphospholipid antibodies. The occurrence and development of APS are complex and associated with immune disorders, with its prognosis remaining uncertain. Owing to its pathogenesis, anticoagulation therapy is the primary treatment for patients with APS. In recent years, with increased attention on APS, research on its treatment strategies has flourished, and preclinical and clinical relevance studies are being conducted to re‑evaluate the mechanism of action of existing drugs and to develop new drugs. Recent evidence suggests that vitamin D (VD) may help improve immune disorders in patients with APS by regulating the balance between immune cells. In this review, the potential mechanistic role of VD in APS protection was discussed, highlighting the potential effects of VD as a promising adjuvant treatment option for APS.

Mental stress may lead to ovarian dysfunction. Psychological stress disrupts ovarian function, leading to adverse in vitro fertilization outcomes, premature ovarian insufficiency and decreased ovarian reserve. Furthermore, psychological stress caused by decreased ovarian function and infertility can exacerbate the mental burden. In animals, psychological stress leads to ovarian insufficiency, resulting in irregular estrous cycles and decreased ovarian reserve. The present study summarizes effects of psychogenic stress on ovarian function and the underlying mechanisms, highlighting involvement of the hypothalamic‑pituitary‑adrenal, sympathetic‑adrenal‑medullary and hypothalamic‑pituitary‑ovarian axes, as well as the neuroendocrine‑metabolic network. Moreover, the present review outlines psychological intervention and metabolic strategies for improving ovarian function, offering potential new approaches for treating ovarian hypofunction. The present study aims to clarify understanding of psychological stress‑induced ovarian dysfunction and propose alternative intervention strategies for ovarian dysfunction and infertility.

Following the publication of the above article, an interested reader drew to the Editor's attention that various of the histological structural images shown in Fig. 5 on p. 190 were strikingly similar to data that were featured in Fig. 1A of a previous paper by the same research group that appeared in the Journal Laboratory Animal Research. On re‑examining their original data, the authors confirmed that an error occurred during the paper submission/production process, and that Fig. 5 did not appear in the above article as the authors had intended. The correct version of Fig. 5, containing the data that the authors intended for inclusion in this article, is shown on the next page. Also shown is a corrected version of Table II corresponding to the replacement version of Fig. 5, containing data that are derived from an analysis of the data shown in this figure. Furthermore, the replacement of the images in Fig. 5, and the revisions of the data made in Table II, also dictate that the following changes are needed to be made in the main text of the paper (all associated with Results section on p. 191, 'Recovery effect of EtRLP on histological alterations of the transverse colon' subsection): The sentences in lines 9‑14 of this section should now read as following (changes from the original text are highlighted in bold): 'Following Lop+EtRLP or Lop+Bisac treatments, the villus length increased by 270‑290% relative to the Lop+Vehicle‑treated group (Fig. 5 and Table II). Furthermore, the alterations in muscle thickness were similar to those in villus length, although crypt layer thickness only increased by 145‑150% relative to the Lop+Vehicle‑treated group (Fig. 5 and Table II)'. Note that the errors made during the assembly of Fig. 5 and Table II did not grossly affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 185‑198, 2019; DOI: 10.3892/ijmm.2018.3960].

Despite significant progress in managing multiple myeloma (MM) in recent years, certain patients still have a short duration of therapeutic response, often relapsing within 18 months. These patients typically have high‑risk genetic mutations and may show little to no response to current treatments, highlighting the need for further exploration of optimal therapeutic targets for MM. B‑cell maturation antigen (BCMA), highly expressed in mature B lymphocytes and plasma cells and upregulated in MM, is a promising therapeutic target. Various BCMA‑targeted strategies, including antibody‑drug conjugates, bispecific T‑cell engagers and chimeric antigen receptor T‑cell therapy, are under clinical evaluation to optimize efficacy and safety. This review summarizes the latest clinical updates on these strategies, highlights their effectiveness in MM and relapsed/refractory MM and provides future perspectives and recommendations for overcoming current challenges.

Cellular immunotherapy represents a pivotal treatment modality in clinical practice. Regulatory B cells (Bregs), a key subset of B lymphocytes, hold promise in the management of autoimmune diseases, cancer and transplantation immunity. The expansion of Bregs for cell therapy is a promising strategy to alleviate inflammation and promote immune tolerance. Achieving immune tolerance relies on balance between regulatory and effector cells. One primary objective of cellular therapy is to shift this balance towards Bregs, fostering a more tolerant immune microenvironment. The adoptive transfer of Bregs not only increases their quantity but also modulates the number and function of other immune cells. Maximizing in vitro expansion of Bregs and enhancing their regulatory functions are key focuses in transplant immunology. However, the precise mechanisms underlying the in vitro expansion of IL‑10‑secreting B cells (B10) remain inadequately understood. The present review aims to provide a comprehensive overview of the signaling pathways involved in B10 activation and expansion, as well as to highlight the techniques for in vitro amplification and development of adoptive B10 therapy in transplantation, which aims to advance the field of cellular therapy targeting Bregs.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited therapeutic options. Cisplatin is a primary chemotherapeutic agent utilized in combination with other drugs or radiotherapy for PDAC treatment. However, the severe side effects of cisplatin often necessitate discontinuation of therapy and drug resistance in tumor cells poses significant clinical challenges. Therefore, the development of effective therapeutic strategies is imperative. The present study investigated whether repositioning of the antipsychotic drug aripiprazole could sensitize the anticancer activity of cisplatin in pancreatic cancer at doses calculated by the combination index. The findings indicated that aripiprazole combined with cisplatin to suppress pancreatic cancer cell growth. Notably, the combination notably increased the expression of apoptosis markers, including cleaved caspase‑3, compared with cisplatin alone. Additionally, this combination effectively decreased XIAP and MCL‑1 expression via mitochondrial membrane potential change as revealed by JC‑1 assay, thereby inducing apoptosis. Furthermore, in fluid shear stress assay, the combination of aripiprazole and cisplatin notably inhibited cell adhesion and tumor spheroid formation. Mechanistically, phospho‑kinase array profiles showed that the enhanced anticancer efficacy of the combination treatment could be attributed to the inhibition of STAT3 signaling, which led to a significant reduction in tumor growth in a pancreatic cancer animal model. The results showed that the repositioning of aripiprazole inhibits cancer cell growth by blocking the STAT3 signaling pathway and effectively enhancing cisplatin‑induced apoptosis, thereby suggesting that the combination of aripiprazole and cisplatin may be a potent chemotherapeutic strategy for the treatment of pancreatic cancer.

Following the publication of this paper, a concerned reader drew to the Editor's attention that it appeared as if the authors had calculated the apoptotic rates erroneously. The authors were asked to provide an explanation to account for the concerns raised by the interested reader; however, they did not respond to this request submitted by the Editorial Office. Therefore, owing to the lack of responsiveness on the part of the authors, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the journal. The Editor would like to apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 973‑981, 2019; DOI: 10.3892/ijmm.2019.4258].

Cell senescence impedes the self‑renewal and osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs), thus limiting their application in tissue regeneration. The present study aimed to elucidate the role and mechanism of repetitive element (RE) activation in BMSC senescence and osteogenesis, as well as the intervention effect of quercetin. In an H2O2‑induced BMSC senescence model, quercetin treatment alleviated senescence as shown by a decrease in senescence‑associated β‑galactosidase (SA‑β‑gal)‑positive cell ratio, increased colony formation ability and decreased mRNA expression of p21 and senescence‑associated secretory phenotype genes. DNA damage response marker γ‑H2AX increased in senescent BMSCs, while expression of epigenetic markers methylation histone H3 Lys9, heterochromatin protein 1α and heterochromatin‑related nuclear membrane protein lamina‑associated polypeptide 2 decreased. Quercetin rescued these alterations, indicating its ability to ameliorate senescence by stabilizing heterochromatin structure where REs are primarily suppressed. Transcriptional activation of REs accompanied by accumulation of cytoplasmic double‑stranded (ds)RNA, as well as triggering of the RNA sensor retinoic acid‑inducible gene I (RIG‑I) receptor pathway in H2O2‑induced senescent BMSCs were shown. Similarly, quercetin treatment inhibited these responses. Additionally, RIG‑I knockdown led to a decreased number of SA‑β‑gal‑positive cells, confirming its functional impact on senescence. Induction of senescence or administration of dsRNA analogue significantly hindered the osteogenic capacity of BMSCs, while quercetin treatment or RIG‑I knockdown reversed the decline in osteogenic function. The findings of the current study demonstrated that quercetin inhibited the activation of REs and the RIG‑I RNA sensing pathway via epigenetic regulation, thereby alleviating the senescence of BMSCs and promoting osteogenesis.

The present study investigated the anti‑melanogenesis effects of Giant Centella asiatica (GCA), a new cultivator of Centella asiatica (CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.