The future of diabetic wound healing: unveiling the potential of mesenchymal stem cell and exosomes therapy.

Diabetes mellitus (DM) is a significant public health problem and is one of the most challenging medical conditions worldwide. It is the severe complications that make this disease more intricate. A diabetic wound is one of these complications. Patients with diabetes are at higher risk of developing diabetic foot ulcers (DFU). Due to the ineffectiveness of Conventional treatments, growth in limb amputation, morbidity, and mortality have been recognized, which indicates the need for additional treatment. Mesenchymal stem cells (MSCs) can significantly improve wound healing. However, there are some risks related to stem cell therapy. Exosome therapy is a new treatment option for diabetic wounds that has shown promising results. However, an even more advanced form called cell-free therapy using exosomes has emerged. This upgraded version of stem cell therapy offers improved efficacy and eliminates the risk of cancer progression. Exosome therapy promotes wound healing from multiple angles, unlike traditional methods that primarily rely on the body's self-healing ability and only provide wound protection. Therefore, exosome therapy has the potential to replace conventional treatments effectively. However, further research is necessary to distinguish the optimal type of stem cells for therapy, ensure their safety, establish appropriate dosing, and identify the best management trail. The present study focused on the current literature on diabetic wound ulcers, their treatment, and mesenchymal stem cell and exosome therapy potential in DFU.

Comparison of letrozole with gonadotropin-releasing hormone agonist in frozen embryo transfer after recurrent implantation failure: An RCT.

BACKGROUND: The use of frozen embryo transfer (FET) is increasing worldwide in the treatment of infertility by in vitro fertilization. Different methods of endometrial preparation for FET have been suggested. OBJECTIVE: The aim of this study was to compare the pregnancy outcomes after treatment with letrozole and those after treatment with the combination of gonadotropin-releasing hormone (GnRH) agonist and estradiol in FET. MATERIALS AND METHODS: This randomized controlled trial study was conducted on 142 infertile women with a history of previous FET failure. Participants were randomly assigned to two groups (n = 71 each). The GnRH group received 500 µg of buserelin plus 4mg estradiol (which increased to 8 mg if endometrial thickness was less than 5 mm), and the letrozole group received 5 mg of letrozole plus 75 IU of recombinant human follicle-stimulating hormone). At least two high-quality embryos were transferred to each subject in both groups. The outcome measures were clinical pregnancy rate and fetal heart rate detection. RESULTS: Subjects in the study groups had similar demographic characteristics and baseline clinical condition. Mean endometrial thickness in the letrozole and GnRH agonist groups were 8.90 ± 0.88 mm and 8.99 ± 0.85 mm, respectively (p = 0.57). The number of positive results of the beta human chorionic gonadotropin test and detection of fetal heartbeat were not significantly different between the groups (p > 0.05). CONCLUSION: The administration of letrozole and GnRH may produce similar pregnancy outcomes in FET.

Hereditary thrombophilia genetic variants in recurrent pregnancy loss.

BACKGROUND: The relationship between thrombophilia genes and recurrent pregnancy loss has been discussed. The aim of this study was to investigate the association between of MTHFR C677T, A1298C, F2G20210A, and F5 G1691A genetic variants among Iranian women with recurrent miscarriage. METHODS: A total of 245 women with two or more recurrent pregnancy loss, with mean age years were enrolled in the study. To compare genotypes, we have selected 250 healthy women without history of miscarriage as control group. Genomic DNA of participants was evaluated using polymerase chain reaction followed by Sanger sequencing to determine the genotype frequency. RESULTS: The mean age were 32.16 ± (21-42) and 31.81 ± (19-40) for case and control groups respectively. MTHFR C677T and A1298C mutant alleles were found to be significantly more prevalent in patients than control. However, F2G20210A and F5 G1691A genetic variants showed no significance. CONCLUSION: The allele frequencies for the assessed genotypes in this study are consistent with the data obtained for other countries. We observed significant susceptible effects of MTHFR C677T, and A1298C among participants. According to the relatively high prevalence of these variants, we recommend genetic testing for women with RPL before therapeutic decisions.

Association of IL-1 and TNF-α Levels in Endometrial Secretion and Success of Embryo Transfer in IVF/ICSI Cycles.

BACKGROUND: In this work, we have determined the levels of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), which function as cytokines in endometrial receptivity, through the endometrial secretion within the eligible individuals and thus studied their relationships with the success or failure of pregnancy in in vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) cycles. MATERIALS AND METHODS: In this prospective study, 76 women were selected for their first IVF/ICSI and met the study inclusion criteria. All of the patients have undergone the endometrial secretion aspiration prior to performing the oocyte collection. The levels of IL-1and TNF-α were analyzed by the means of enzyme-linked immunosorbent assay method, using special standard kits. The patients were requested to undergo the serum human chorionic gonadotropin measurements and ultrasound evaluation for the purpose of detecting successful implantations and pregnancies. RESULTS: Among the 76 subjects of the study, 33 (43.4%) patients had a positive beta-human chorionic gonadotropin (ß-hCG) and 44 (56.6%) resulted in a negative ß-hCG. It should be also noted that through the patients with positive ß-hCG, 23 (30.3%) of them displayed fetal heart rate in their transvaginal sonography (TVS). Compared to the group with failed pregnancies and their cytokine levels, we perceived a higher concentration of IL-1 in the group containing successful chemical pregnancies (P=0.00). However, there was no significant difference in terms of clinical pregnancy in the IL-1 levels between the two groups (P=0.06). In addition, there was not any notable difference in the levels of TNF-α between the two groups, neither in terms of chemical nor clinical pregnancy (P=0.8 and P=0.6, respectively). CONCLUSION: The current study suggests that higher concentrations of IL-1 in endometrial secretions could be associated with improved endometrial receptivity and IVF outcome. With regards to TNF-α, no statistically significant difference was observed between the groups of with and without successful pregnancies.

Lymphatic mapping and sentinel node biopsy in squamous cell carcinoma of the vulva: systematic review and meta-analysis of the literature.

OBJECTIVES: We reviewed the available literature on the accuracy of sentinel node (SN) mapping in the inguinal lymph node staging of vulvar squamous cell carcinoma (SCC). METHODS: Medline and SCOPUS were searched by using "sentinel AND vulv*" as key words. Studies evaluating the accuracy of SN mapping in the inguinal lymph node staging of vulvar SCC were included if enough data could be extracted for calculation of detection rate and/or sensitivity. Only studies validated by inguinal lymph node dissection were included for sensitivity meta-analysis. RESULTS: Forty-nine studies were included in the systematic review. Pooled patient and groin basis SN detection rates were 94.4% [92.4-95.9] and 84.6% [80.5-88], respectively. Pooled patient and groin basis sensitivity were 92% [90-95] and 92% [89-94], respectively (or 8% [5-10] and 8% [6-11] false negative rates). Pooled negative predictive values were 97% [96-98] and 98% [97-99] for patient and groin basis analyses respectively. SN detection rate and sensitivity were related to mapping method (blue dye, radiotracer, or both) and location of the tumor (midline vs. lateral tumors). Patients with palpable inguinal nodes had lower detection rate and sensitivity. CONCLUSION: SN mapping is an accurate method for inguinal node staging in vulvar SCC. Combining radiotracer and blue dye methods and excluding patients with palpable inguinal nodes result in the highest detection rate and sensitivity. For midline tumors possible false negative results of SN mapping should be taken into account.