Connexins in epidermal health and diseases: insights into their mutations, implications, and therapeutic solutions.

The epidermis, the outermost layer of the skin, serves as a protective barrier against external factors. Epidermal differentiation, a tightly regulated process essential for epidermal homeostasis, epidermal barrier formation and skin integrity maintenance, is orchestrated by several players, including signaling molecules, calcium gradient and junctional complexes such as gap junctions (GJs). GJ proteins, known as connexins facilitate cell-to-cell communication between adjacent keratinocytes. Connexins can function as either hemichannels or GJs, depending on their interaction with other connexons from neighboring keratinocytes. These channels enable the transport of metabolites, cAMP, microRNAs, and ions, including Ca2+, across cell membranes. At least ten distinct connexins are expressed within the epidermis and mutations in at least five of them has been linked to various skin disorders. Connexin mutations may cause aberrant channel activity by altering their synthesis, their gating properties, their intracellular trafficking, and the assembly of hemichannels and GJ channels. In addition to mutations, connexin expression is dysregulated in other skin conditions including psoriasis, chronic wound and skin cancers, indicating the crucial role of connexins in skin homeostasis. Current treatment options for conditions with mutant or altered connexins are limited and primarily focus on symptom management. Several therapeutics, including non-peptide chemicals, antibodies, mimetic peptides and allele-specific small interfering RNAs are promising in treating connexin-related skin disorders. Since connexins play crucial roles in maintaining epidermal homeostasis as shown with linkage to a range of skin disorders and cancer, further investigations are warranted to decipher the molecular and cellular alterations within cells due to mutations or altered expression, leading to abnormal proliferation and differentiation. This would also help characterize the roles of each isoform in skin homeostasis, in addition to the development of innovative therapeutic interventions. This review highlights the critical functions of connexins in the epidermis and the association between connexins and skin disorders, and discusses potential therapeutic options.

Author Correction: The clinical significance and diagnostic value of serum Dickkopf1 and CKAP4 levels in patients with gastric cancer: a prospective study.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (20): 10031-10040-DOI: 10.26355/eurrev_202310_34183-PMID: 37916373-published online on October 27, 2023. After publication, the authors found a mistake in Table I. Under Table I, the following sentence "HR: hazard ratio. CI: confidence interval. SCC: squamous cell carcinoma. FIGO: International Federation of Gynecology and Obstetrics. DFS: disease-free survival. OS: overall survival. p<0.05 and p<0.01 values were accepted for the significance level of the test" has been mistakenly inserted and must be removed. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34183.

The clinical significance and diagnostic value of serum Dickkopf1 and CKAP4 levels in patients with gastric cancer: a prospective study.

OBJECTIVE: Gastric cancer is diagnosed at an advanced stage in most patients, and the prognosis is poor. Novel biochemical markers of high diagnostic value for the detection of the disease are therefore important. Dickkopf1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) have been extensively studied as biomarkers in cancer patients. PATIENTS AND METHODS: Serum DKK1 and CKAP4 levels in 58 patients with gastric cancer and 41 healthy controls were examined using an ELISA kit in this prospective study. The patients were subdivided into groups based on pathological TNM staging and histological grades. Serum levels of both proteins in the patients with gastric cancer were measured preoperatively, 10 and 30 days after surgery. RESULTS: Serum DKK1 and CKAP4 levels were significantly higher in the gastric cancer group compared to the healthy controls (p<0.05). Serum levels of both proteins increased in line with the pathological stage and histological grade of the gastric cancer. Serum CKAP4 and DKK1 levels decreased after surgical resection. Both serum levels also decreased significantly on day 30 after surgery compared to day 10 (p<0.05). Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) positivity rates were below 20% in the gastric cancer group, while the diagnostic value (sensitivity and specificity) of serum CKAP-4 and DKK1 exceeded 80%. CONCLUSIONS: DKK1 and CKAP4 are biomarkers of high diagnostic value that can be used to diagnose and predict the severity of gastric cancer. These proteins can also be employed for disease monitoring after surgical resection. The diagnostic value of these proteins is higher than that of biomarkers such as CEA and CA19-9, which are routinely used in clinical practice.

The diagnostic role of preoperative blood tests in complicated appendicitis: A feasible approach to surgical decision.

Background: An accurate diagnosis and timely surgical intervention have significant importance in noncomplicated appendicitis (NCA) and complicated appendicitis (CA). Therefore, any factor that helps in the prediction of CA also contributes to suitable treatment options. Aim: This retrospective study aimed to identify any relationship between acute appendicitis (AA) and preoperative blood test levels and whether these parameters can differentiate between NCA and CA patients. Patients and Methods: A database of 201 appendectomies and 100 control healthy patients was analyzed between 2019 and 2022. Patients were divided into three groups: NCA without peritonitis or phlegmonous appendicitis as group 1; CA with perforated, necrotizing appendicitis with peritonitis as group 2; and the healthy control group (CG) as group 3. White blood cell (WBC), platelet distribution width (PDW), mean platelet volume (MPV), red cell distribution width (RDW), creatine kinase (CK), and bilirubin levels were collected from the patients and compared statistically between the groups. Results: Age, WBC, and PDW levels were set as predictive in the differential diagnosis of CA as a result of receiver operating characteristic (ROC) analysis. The multivariate analysis demonstrated that age (OR: 1.023; 95% CI: 1.000-1.045; P = 0.04), male sex (OR: 3.718; 95% CI: 1.501-9.213; P = 0.005), WBC levels (OR: 1.000; 95% CI: 1.000-1.000; P = 0.002), and PDW levels (OR: 2.129; 95% CI: 1.301-3.484; P = 0.003) were independently associated with CA. Conclusion: Age, higher WBC count, and PDW levels are valuable in differentiating the diagnosis of CA from NCA, and this could be a feasible approach for surgical decisions.

Polyploidy Phenomenon as a Cause of Early Miscarriages in Abortion Materials.

Objectives: Chromosomal abnormalities are an important cause of especially early miscarriages. The aim of this study was to analyze the chromosomal aberrations and determine the frequencies of numerical and structural chromosome abnormalities in spontaneous abortion materials. Methods: This was a prospective research and ninety two abortion samples obtained from women who had one or more miscarriages were included in the study. Conventional karyotype analysis was performed on each sample to identify possible chromosomal abnormalities. Results: By karyotype analysis, 11 polyploidy cases, (9 triploids and 2 tetraploids), 8 trisomies (one of which was mosaic), 2 monosomies (monosomy X), 1 isochromosome, 1 Xq deletion, and 4 translocations were detected in abortion materials. Isochromosome and Xq deletion cases were also mosaic. In addition, five polymorphic variants were revealed. We found higher paternal age in polyploidy cases. Conclusion: The most common anomaly we found in abortion materials was polyploidy. This was followed by aneuploidy (trisomy and monosomy). Polyploidy (triploidy or tetraploidy) emerged as an important cause in cases of spontaneous abortion. Paternal age may be associated with polyploidy especially triploidy.

The effect of mesh fixation on migration and postoperative pain in laparoscopic TEP repair: prospective randomized double-blinded controlled study.

PURPOSE: The development of chronic pain is one of the major post-surgery problems after inguinal hernia repair. Although the possibility of chronic pain formation decreases with laparoscopic methods, pain may develop due to the staples used. It is thought that absence of mesh fixation in total extra-peritoneal (TEP) repair does not increase the recurrence rate. This study aims to investigate the absence of mesh fixation in the TEP on the development of postoperative pain, mesh displacement, and recurrence rate. METHODS: Between December 2019 and December 2020, 100 patients who underwent TEP repair due to unilateral inguinal hernia in the General Surgery Clinic of Hitit University were included in the study. Study was registered at http://Clinicaltrials.gov (NCT05152654). Patients were divided into two groups as repairs in which the mesh was fixed with a tacker and no-fixation (NF) was used. The mesh is marked with radiopaque clips. Patients were compared in terms of postoperative pain, mobilization time, hospital stay, return to work, chronic pain, early-late mesh displacement, and recurrence. RESULTS: While there was no significant difference between the groups in terms of mesh displacement and recurrence, it was observed that the NF group developed significantly less pain in the early and late postoperative period compared to the other group. The time-dependent reduction rate of postoperative pain was higher in NF group than in other group. In addition, operation time was shorter in the NF group. CONCLUSION: While the absence of mesh fixation in TEP hernia repair does not increase the recurrence rate, it can be used safely, because it causes less acute and chronic pain. TRAIL REGISTRATION: Clinicaltrials number: NCT05152654.

Synthetic MR Imaging-Based WM Signal Suppression Identifies Neonatal Brainstem Pathways in Vivo.

BACKGROUND AND PURPOSE: Multidynamic multiecho sequence-based imaging enables investigators to reconstruct multiple MR imaging contrasts on the basis of a single scan. This study investigated the feasibility of synthetic MRI-based WM signal suppression (syWMSS), a synthetic inversion recovery approach in which a short TI suppresses myelin-related signals, for the identification of early myelinating brainstem pathways. MATERIALS AND METHODS: Thirty-one cases of neonatal MR imaging, which included multidynamic multiecho data and conventionally acquired T1- and T2-weighted sequences, were analyzed. The multidynamic multiecho postprocessing software SyMRI was used to generate syWMSS data (TR/TE/TI = 3000/5/410 ms). Two raters discriminated early myelinating brainstem pathways (decussation of the superior cerebellar peduncle, medial lemniscus, central tegmental tract, and medial longitudinal fascicle [the latter 3 assessed at the level of the pons]) on syWMSS data and reference standard contrasts. RESULTS: On the basis of syWMSS data, the decussation of the superior cerebellar peduncle (31/31); left/right medial lemniscus (31/31; 30/31); left/right central tegmental tract (19/31; 20/31); and left/right medial longitudinal fascicle (30/31) were reliably identified by both raters. On the basis of T1-weighted contrasts, the decussation of the superior cerebellar peduncle (14/31); left/right medial lemniscus (22/31; 16/31); left/right central tegmental tract (1/31); and left/right medial longitudinal fascicle (9/31; 8/31) were reliably identified by both raters. On the basis of T2-weighted contrasts, the decussation of the superior cerebellar peduncle (28/31); left/right medial lemniscus (16/31; 12/31); left/right central tegmental tract (23/31; 18/31); and left/right medial longitudinal fascicle (15/31; 14/31) were reliably identified by both raters. CONCLUSIONS: syWMSS data provide a feasible imaging technique with which to study early myelinating brainstem pathways. MR imaging approaches that use myelin signal suppression contribute to a more sensitive assessment of myelination patterns at early stages of cerebral development.

Different from the Beginning: WM Maturity of Female and Male Extremely Preterm Neonates-A Quantitative MRI Study.

BACKGROUND AND PURPOSE: Former preterm born males are at higher risk for neurodevelopmental disabilities compared with female infants born at the same gestational age. This retrospective study investigated sex-related differences in the maturity of early myelinating brain regions in infants born <28 weeks' gestational age using diffusion tensor- and relaxometry-based MR imaging. MATERIALS AND METHODS: Quantitative MR imaging sequence acquisitions were analyzed in a sample of 35 extremely preterm neonates imaged at term-equivalent ages. Quantitative MR imaging metrics (fractional anisotropy; ADC [10-3mm2/s]; and T1-/T2-relaxation times [ms]) of the medulla oblongata, pontine tegmentum, midbrain, and the right/left posterior limbs of the internal capsule were determined on diffusion tensor- and multidynamic, multiecho sequence-based imaging data. ANCOVA and a paired t test were used to compare female and male infants and to detect hemispheric developmental asymmetries. RESULTS: Seventeen female (mean gestational age at birth: 26 + 0 [SD, 1 + 4] weeks+days) and 18 male (mean gestational age at birth: 26 + 1 [SD, 1 + 3] weeks+days) infants were enrolled in this study. Significant differences were observed in the T2-relaxation time (P = .014) of the pontine tegmentum, T1-relaxation time (P = .011)/T2-relaxation time (P = .024) of the midbrain, and T1-relaxation time (P = .032) of the left posterior limb of the internal capsule. In both sexes, fractional anisotropy (P [♀] < .001/P [♂] < .001) and ADC (P [♀] = .017/P [♂] = .028) differed significantly between the right and left posterior limbs of the internal capsule. CONCLUSIONS: The combined use of various quantitative MR imaging metrics detects sex-related and interhemispheric differences of WM maturity. The brainstem and the left posterior limb of the internal capsule of male preterm neonates are more immature compared with those of female infants at term-equivalent ages. Sex differences in WM maturation need further attention for the personalization of neonatal brain imaging.

The predictive value of platelet/mean platelet volume ratio in predicting colon diverticulitis relapse.

OBJECTIVE: Diverticulitis is a health problem that has increased in frequency recently. It has a wide spectrum from simple inflammation to fecal peritonitis, sepsis and even mortality. Thus, it is important to predict diverticulitis, especially recurrent diverticulitis, and take measures to prevent it. In this study, we investigated the predictive value of the PLT/MPV ratio, which is an inflammation marker in predicting the recurrence of diverticulitis disease. PATIENTS AND METHODS: In this study, 132 patients diagnosed with diverticulitis were analyzed retrospectively. Patients' gender, age, localization of diverticulitis, number of diverticula in computed tomography (CT), hospitalization status, length of hospitalization, control colonoscopies, polyps' number and localizations in colonoscopies, presence of malignancy, need for surgery, and recurrences were not reported. White blood cell (WBC), Neutrophil (NE), Lymphocyte (LY), Hemoglobin (Hb), PLT, MPV, Albumin, Creatine Kinase (CK) and C-reactive protein (CRP) levels were examined. The patients were divided into two groups as those who did not relapse concerning diverticulitis and those who did, and statistical analysis was performed between the two groups about related parameters. RESULTS: Among all patients, recurrence was seen in 11 (10.1%) patients. The patients were divided into two groups according to their recurrence status and statistical significance was sought between the data. The calculated PLT/MPV ratio of patients who did not relapse was 25.61±8.05 and 34.98±11.37 for those who had a relapse (p=0.006). The sensitivity for MPV was 81.8%, a specificity of 57.1% and a cut-off of 9.85. The cut-off value for PLT was 207.5 with 100% sensitivity and 33.7% specificity. A cut-off value of 25.11 was found for PLT/MPV with 100% sensitivity and 49% specificity. CONCLUSIONS: PLT/MPV ratio was significantly higher in relapsed cases. Since it is easily accessible and inexpensive, it will guide physicians for diagnosis concerning early detection of relapse cases and initiation of appropriate treatment.