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1.
Cells ; 13(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38786020

ABSTRACT

A heterogenous population of inflammatory elements, other immune and nonimmune cells and cancer-associated fibroblasts (CAFs) are evident in solid malignancies where they coexist with the growing tumor mass. In highly desmoplastic malignancies, CAFs are the prominent mesenchymal cell type in the tumor microenvironment (TME), where their presence and abundance signal a poor prognosis. CAFs play a major role in the progression of various cancers by remodeling the supporting stroma into a dense, fibrotic matrix while secreting factors that promote the maintenance of cancer stem-like characteristics, tumor cell survival, aggressive growth and metastasis and reduced sensitivity to chemotherapeutics. Tumors with high stromal fibrotic signatures are more likely to be associated with drug resistance and eventual relapse. Identifying the molecular underpinnings for such multidirectional crosstalk among the various normal and neoplastic cell types in the TME may provide new targets and novel opportunities for therapeutic intervention. This review highlights recent concepts regarding the complexity of CAF biology in cholangiocarcinoma, a highly desmoplastic cancer. The discussion focuses on CAF heterogeneity, functionality in drug resistance, contributions to a progressively fibrotic tumor stroma, the involved signaling pathways and the participating genes.


Subject(s)
Cancer-Associated Fibroblasts , Cholangiocarcinoma , Disease Progression , Tumor Microenvironment , Humans , Cholangiocarcinoma/pathology , Cholangiocarcinoma/genetics , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/metabolism , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/metabolism , Animals , Signal Transduction , Drug Resistance, Neoplasm/genetics
2.
Arch Ital Urol Androl ; : 12367, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722147

ABSTRACT

OBJECTIVE: The aim of this study was to investigate whether urinary glycosaminoglycans (GAG) levels reflect clinical status in men with lower urinary tract symptoms and if they could be used as a marker in management of overactive bladder (OAB). METHODS: A total of 34 patients were recruited who were admitted with LUTS and diagnosed as having clinically bladder outlet obstruction (BOO) due to prostate enlargement. These newly diagnosed, never treated patients underwent routine investigation, consisting of history, physical examination, PSA, ultrasound, uroflowmetry, assessment of symptoms scored by both International Prostate Symptom Score (IPSS) and Marmara- Overactive Bladder Questionnaire (M-OBQ). The patients were divided into two groups as those with an initial M-OBQ score < 12 (group 1) and ≥ 13 (group 2). Alfa blocker was initiated in eligible patients. Further evaluations included prostate volume measurement, pre- and post-treatment urinary GAG levels, IPSS and M-QAOB values and maximum urine flow rate (Qmax). RESULTS: Before treatment, urinary GAG level was 21.5 mg/gCr (6.1-45.5) in Group 1, and 23.35 mg/gCr (15.6-32.6) in Group 2 (p =0.845). After the treatment, the GAG level in Group 1 and Group 2 were found to be 19.8 mg/gCr (7.4-70.5) and 18 (7.6- 41.7), respectively (p = 0.511). No difference in GAG levels was found in subgroup analysis for patients with or without OAB. CONCLUSIONS: In recent years, there have been many studies investigating the relationship between LUTS and urinary markers. However, in our prospective study, no relationship was found between pre- and post- treatment urinary GAG levels in patients with LUTS with or without OAB.

3.
Diabetes Res Clin Pract ; 209: 111604, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38447911

ABSTRACT

AIMS: Sodium glucose co-transporter 2 inhibitors (SGLT2is) and/or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with proven cardio- and reno-protective benefits are recommended in people with type 2 diabetes (T2D) at high risk of cardiovascular disease, chronic kidney disease, and/or heart failure. This pooled analysis compared efficacy and safety outcomes of iGlarLixi with or without SGLT2is in people with T2D. METHODS: This post hoc analysis evaluated outcomes in participants who were receiving an SGLT2i when initiating iGlarLixi (SGLT2i users) and those who were not (SGLT2i non-users) in a pooled dataset from three trials: LixiLan-G (advancing from a GLP-1 RA), SoliMix and LixiLan ONE CAN (advancing from basal insulin). RESULTS: Baseline characteristics were generally similar between 219 users and 746 non-users. Least squares mean changes in HbA1c from baseline to Week 26 were similar for users (-1.2 % [95 % confidence intervals: -1.4 %, -1.1 %]) and non-users (-1.2 % [-1.2 %, -1.1 %]). Changes in body weight, fasting glucose and post-prandial glucose were similar between groups, as were hypoglycaemic events. CONCLUSIONS: Pooled results from three studies of adults with T2D demonstrated that iGlarLixi provided similar clinically meaningful improvements in glycaemic control without increased hypoglycaemia risk, regardless of concomitant use of SGLT2is.


Subject(s)
Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Symporters , Adult , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Insulin Glargine/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Blood Glucose , Glycated Hemoglobin , Drug Combinations , Peptides/therapeutic use , Hypoglycemic Agents/adverse effects , Glucagon-Like Peptide 1/therapeutic use , Glucose/therapeutic use , Symporters/therapeutic use , Sodium/therapeutic use , Glucagon-Like Peptide-1 Receptor/agonists
4.
Am J Pathol ; 193(12): 1953-1968, 2023 12.
Article in English | MEDLINE | ID: mdl-37717941

ABSTRACT

Aging is associated with nonresolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a proresolving ligand that acts through the G-protein-coupled receptor called GPR18. Unbiased RNA sequencing revealed increased Gpr18 expression in macrophages from old mice, and in livers from elderly humans, which was associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lacked GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, increased monocyte-derived macrophages, and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly on the bone marrow to increase monocyte-macrophage progenitors. A transplantation assay further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice. Transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, this study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.


Subject(s)
Bone Marrow , Fatty Liver , Middle Aged , Humans , Mice , Animals , Aged , Bone Marrow/metabolism , Receptors, G-Protein-Coupled/metabolism , Aging , Liver Cirrhosis , Fibrosis , Collagen/genetics , Mice, Inbred C57BL
5.
Urol Int ; 107(9): 857-865, 2023.
Article in English | MEDLINE | ID: mdl-37591208

ABSTRACT

INTRODUCTION: Herein, we analyzed the histopathological, oncological and functional outcomes of testis-sparing surgery (TSS) in patients with distinct risk for testicular cancer. METHODS: This is a multicenter retrospective study on consecutive patients who underwent TSS. Patients were categorized in high- or low-risk testicular germ cell tumor (TGCT) according to the presence/absence of features compatible with testicular dysgenesis syndrome. Histology was categorized per size and risk groups. RESULTS: TSS was performed in 83 patients (86 tumors) of them, 27 in the high-risk group. Fifty-nine patients had a non-tumoral contralateral testis present. Sixty masses and 26 masses were benign and TGCTs, respectively. No statistical differences were observed in mean age (30.9 ± 10.32 years), pathological tumor size (14.67 ± 6.7 mm) between risk groups or between benign and malignant tumors (p = 0.608). When categorized per risk groups, 22 (73.3%) and 4 (7.1%) of the TSS specimens were malignant in the high- and low-risk patient groups, respectively. Univariate analysis showed that the only independent variable significantly related to malignant outcome was previous history of TGCT. During a mean follow-up of 25.5 ± 22.7 months, no patient developed systemic disease. Local recurrence was detected in 5 patients and received radical orchiectomy. Postoperative testosterone levels remained normal in 88% of those patients with normal preoperative level. No erectile dysfunction was reported in patients with benign lesions. CONCLUSION: TSS is a safe and feasible approach with adequate cancer control, and preservation of sexual function is possible in 2/3 of patients harboring malignancy. Incidence of TGCT varies extremely between patients at high and low risk for TGCT requiring a careful consideration and counseling.


Subject(s)
Testicular Neoplasms , Urogenital Abnormalities , Male , Humans , Young Adult , Adult , Testis/pathology , Testicular Neoplasms/surgery , Testicular Neoplasms/pathology , Retrospective Studies , Organ Sparing Treatments , Orchiectomy , Urogenital Abnormalities/surgery
6.
J Biochem Mol Toxicol ; 37(10): e23467, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37466109

ABSTRACT

Multidrug resistance (MDR) causes difficulties in the treatment of infections and cancer. Research and development studies have become increasingly important for the strategy of preventing MDR. There is a need for new multitarget drug research and advancement to reduce the development of drug resistance in drug-drug interactions and reduce cost and toxic effects. This study aimed to determine the effects of multi-target triazene compounds on antibacterial, antifungal, antiviral, cytotoxic, and larvicidal activities were investigated in vitro. A series of 12 novel of 1,3-diaryltriazene-substituted sulfadiazine (SDZ) derivatives were synthesized, and the obtained pure products characterized in detail by spectroscopic and analytic methods (FT-IR, 1 H-NMR, 13 C-NMR, and melting points). The antibacterial and antifungal activities of these derivatives (AH1-12) were determined by broth microdilution method. All derivatives have been evaluated in cell-based assays for cytotoxic and antiviral activities against Modified Vaccinia Virus Ankara. The larvicidal efficacy of these chemical compounds was also investigated by using Lucilia sericata (L. sericata) larvae. Twelve 1,3-diaryltriazene-substituted SDZ derivatives (AH1-12) were designed and developed as potent multitargeted compounds. Among them, the AH1 derivative showed the most antibacterial and antifungal activity. Besides, synthesized derivatives AH2, AH3, AH5, and AH7 showed higher antiviral activity than SDZ. All synthesized derivatives showed higher cytotoxic activity than SDZ. Also, they showed larvicidal activity at 72 h of the experiment. As a result, these compounds might be great leads for the development of next-generation multitargeted agents.


Subject(s)
Antineoplastic Agents , Sulfadiazine , Antifungal Agents/pharmacology , Triazenes/chemistry , Triazenes/pharmacology , Spectroscopy, Fourier Transform Infrared , Antineoplastic Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Antiviral Agents/pharmacology , Microbial Sensitivity Tests , Structure-Activity Relationship
7.
Adv Clin Exp Med ; 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37341174

ABSTRACT

BACKGROUND: Renal steatosis is an abnormal accumulation of fat in the kidney and may cause chronic kidney disease (CKD) or CKD progression. OBJECTIVES: This pilot study aimed to evaluate the quantitative measurability of the parenchymal distribution of lipid deposition in the renal cortex and medulla using chemical shift magnetic resonance imaging (MRI) and investigate its relationship with clinical stages in CKD patients. MATERIAL AND METHODS: The study groups included CKD patients with diabetes (CKD-d) (n = 42), CKD patients without diabetes (CKD-nd) (n = 31) and control subjects (n = 15), all of whom underwent a 1.5T MRI of the abdomen using the Dixon two-point method. The fat fraction (FF) values in the renal cortex and medulla were calculated from measurements made on Dixon sequences, and then compared between the groups. RESULTS: The cortical FF value was higher than the medullary FF value in control (0.057 (0.053-0.064) compared to 0.045 (0.039-0.052)), CKD-nd (0.066 (0.059-0.071) compared to 0.063 (0.054-0.071)), and CKD-d (0.081 (0.071-0.091) compared to 0.069 (0.061-0.077)) groups (all p < 0.001). The CKD-d group cortical FF values were higher than those of the CKD-nd group (p < 0.001). The FF values began increasing at CKD stages 2 and 3, and reached statistical significance at stages 4 and 5 in CKD patients (p < 0.001). CONCLUSIONS: Renal parenchymal lipid deposition can be quantified separately in the cortex and medulla using chemical shift MRI. Fat accumulation occurred in cortical and medullary parenchyma in CKD patients, though predominantly in the cortex. This accumulation increased proportionally with the disease stage.

8.
Curr Med Imaging ; 2023 May 22.
Article in English | MEDLINE | ID: mdl-37272460

ABSTRACT

BACKGROUND: DWI and ADC-mapping was performed to analyze hepatic metastasis of GIST, GEP-NET. OBJECTIVE: The objective of this study is to present hepatic metastasis of GIST and GEP-NET with Diffusion weighted MR imaging(DWI) and the Apparent diffusion coefficients (ADC) values of masses. METHOD: 18 GIST patients and 8 GEP-NET patients were examined retrospectively. 11 males and 6 females were present in GIST group, 7 males to 5 females were involved in GEP-NET group. 18 primary GIST and 10 hepatic metastasis of GIST, 8 original GEP-NET and 19 hepatic metastasis of GEP-NET; total 55 GIST and GEP-NET masses were analysed by ADC mapping. MR images were acquired by 1,5 T MR units (32 mT/min gradient strength- Achieva; Philips Healthcare, Best, Netherlands and 32 channel GE Signa GE-Wisconsin-USA); by using a 4-8 channel standard phased-array torso XL coil, all images were evaluated by an Abdominal MRI experienced radiologist. DWI was performed in the transverse plane by using spin-echo-planar imaging sequence. RESULT: No statistical differences were observed between GIST and GEP-NET patients according to age and gender variations. No significant statistical differences were observed according to the diameters and ADC values of GIST and GEP-NET patients. A significant statistical difference was observed between GIST and GEP-NET groups in terms of size of liver metastasis which was significantly higher in GIST patients. All three groups (GIST_Hep. MET, GEP-NET_Liver_Met and normal) were statistically differed according to ADC values. With the ROC curve analysis: Hepatic metastasis of GIST(n=10) and normal liver (n:47) had cut-off value for ADC: 0.925 under AUC: 0.939 with regard to ADC values and regarded 89.4 % Sensitivity, 100% Specificity, 100% PPV and 66.7% PPV. ROC curve of GEP NET_ Hepatic metastasis (n=19) group and normal liver (n:47) group presented cut-off value for ADC: 0.860 under AUC: 0.967 correlated to ADC values with 93.6 % sensitivity, 89.5% specificity, 95.7% PPV and 85% PPV. CONCLUSION: High cellular tumors resulted from liver metastasis of GIST and GEP-NET's, and a positive correlation was observed between ADC values and cellularity/differentiation ratios of metastatic masses.

9.
Neurosurg Focus ; 54(5): E8, 2023 05.
Article in English | MEDLINE | ID: mdl-37127028

ABSTRACT

OBJECTIVE: Despite the relatively high success of surgical clipping of supraclinoid segment aneurysms of the internal carotid artery (ICA), flow diverter (FD) stent therapy is becoming increasingly used for these aneurysms. This study aims to evaluate the characteristics of FD placement for unruptured ICA supraclinoid segment aneurysms at 6 different centers with different experience levels in Türkiye. METHODS: In this retrospective, multicenter study, the authors reviewed the demographic information, aneurysm shape/dimensions (neck, aspect ratio, dome/neck ratio, and maximum diameter), preoperative antiplatelet regimen, FD stent brand, perioperative complications, intervention time, clinical (modified Rankin Scale) and radiological (O'Kelly-Marotta [OKM] grading scale) outcomes, and follow-up time of 54 patients. RESULTS: A total of 55 interventions for 61 aneurysms (58 supraclinoid ICA aneurysms) were performed in the 54 patients included in the study. The female/male ratio in this population was 44/10, and the mean age was 53.5 ± 13.6 (range 21-82) years. The most common form and location of the aneurysms were saccular 91.4% (53/58) and ophthalmic segment 69% (40/58), respectively. The preferred antiplatelet regimen was acetylsalicylic acid plus ticagrelor 50% (27/54). The overall complication rate was 25.5% (14/55), and the mean follow-up time was 25.76 ± 17.88 months. The successful radiological outcome (OKM grade C or D) rate at the 6-month follow-up was 92.6%. No perioperative complications led to any permanent or transient neurological deficit. CONCLUSIONS: The results of this first multicenter study evaluating FD stent use for unruptured ICA supraclinoid segment aneurysms showed that FD stent treatment is a feasible method for replacing clipping and coil embolization with manageable complications and a high success rate.


Subject(s)
Endovascular Procedures , Intracranial Aneurysm , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Carotid Artery Diseases , Carotid Artery, Internal/surgery , Embolization, Therapeutic/methods , Endovascular Procedures/methods , Intracranial Aneurysm/surgery , Retrospective Studies , Stents/adverse effects , Treatment Outcome
10.
J Biochem Mol Toxicol ; 37(8): e23375, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37129082

ABSTRACT

Schiff bases (imines or azomethines) are versatile ligands synthesized from the condensation of amino compounds with active carbonyl groups and used for many pharmaceutical and medicinal applications. In our study, we aimed to determine the cytotoxic, antifungal and larvicidal activities of biologically potent bis-sulfonamide Schiff base derivatives that were re-synthesized by us. For this aim, 16 compounds were re-synthesized and tested for their cytotoxic, antifungal and larvicidal properties. Among this series, compounds A1B2, A1B4, A4B2, A4B3, and A4B4 were shown to have cytotoxic activity against tested cancer lung cell line (A549). The most potent antifungal activity was observed in compounds A2B1 and A2B2 against all fungi. A1B1 showed the strongest larvicidal effect at all concentrations at the 72nd h (100% mortality). These obtained results demonstrate that these type of bis-substituted compounds might be used as biologically potent pharmacophores against different types of diseases.


Subject(s)
Antifungal Agents , Schiff Bases , Antifungal Agents/pharmacology , Schiff Bases/pharmacology , Fungi , Sulfanilamide , Cell Line , Microbial Sensitivity Tests
11.
Curr Oncol ; 30(2): 2388-2404, 2023 02 16.
Article in English | MEDLINE | ID: mdl-36826143

ABSTRACT

Immunotherapy has remained at the vanguard of promising cancer therapeutic regimens due to its exceptionally high specificity for tumor cells and potential for significantly improved treatment-associated quality of life compared to other therapeutic approaches such as surgery and chemoradiation. This is especially true in the digestive system, where high rates of mutation give rise to a host of targetable tumor-specific antigens. Many patients, however, do not exhibit measurable improvements under immunotherapy due to intrinsic or acquired resistance, making predictive biomarkers necessary to determine which patients will benefit from this line of treatment. Many of these biomarkers are assessed empirically by pathologists according to nuanced scoring criteria and algorithms. This review serves to inform clinicians and pathologists of extant and promising upcoming biomarkers predictive of immunotherapeutic efficacy among digestive system malignancies and the ancillary testing required for interpretation by pathologists according to tumor site of origin.


Subject(s)
Digestive System Neoplasms , Precision Medicine , Humans , Quality of Life , Biomarkers, Tumor/genetics , Mutation
12.
J Coll Physicians Surg Pak ; 33(1): 20-26, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36597230

ABSTRACT

OBJECTIVE: To evaluate the late gadolinium enhancement ratio (LGER) quantitatively in late post-contrast images in multiparametric prostate MRI (mpMRI) for the differential diagnosis of chronic prostatitis and prostate cancer (PCa). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Radiology, Suleyman Demirel University, Isparta, Turkey, from January 2018 to October 2021. METHODOLOGY: The data of 111 patients with a diagnosis of PCa and chronic prostatitis, were retrospectively analysed who underwent mpMRI of the prostate were retrospectively analysed. Histopathological verification was available in 57 of 57 prostate carcinoma patients and 20 of 54 chronic prostatitis cases. The detection of lesions from the images and the correlation of the detected lesions with their histopathological diagnoses were made by the joint decision of two radiologists. The LGER measurements were made independently by both radiologists. Signal intensity (SI) values of the lesions were obtained by placing a hand-drawn ROI on pre-contrast and late post-contrast images. Late enhancement ratio was calculated from the ratio of the difference between the pre- and post-contrast SI values to the pre-contrast SI values. The LGER values obtained were statistically compared between the pathologically proven PCa and chronic prostatitis patient groups. RESULTS: The prostatitis LGER values (103.40 ± 31.54%) were significantly higher than the PCa values (79.71±27.39, p<0.001). The LGER values of lesions with a Gleason score <7 were lower than those of lesions scoring ≥7 (p = 0.004). The LGER values of PI-RADS-3 PCa lesions were lower than those of PI-RADS-4 and PI-RADS-5 (p = 0.002). In the late post-contrast phase, low signal measurements in PI-RADS-3 lesions excluded the presence of prostatitis. CONCLUSION: Late contrast enhancement quantitative SI measurements performed in the late contrast phase of mpMRI may enable the differential diagnosis of PCa/prostatitis and a more accurate evaluation of PI-RADS scores in terms of malignancy. KEY WORDS: Prostate cancer, Prostatitis, Gadolinium, Dynamic contrast-enhanced magnetic resonance imaging.


Subject(s)
Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Prostatitis , Male , Humans , Multiparametric Magnetic Resonance Imaging/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging/methods , Prostatitis/diagnostic imaging , Contrast Media , Gadolinium , Diagnosis, Differential , Retrospective Studies
13.
Turk Neurosurg ; 33(1): 110-117, 2023.
Article in English | MEDLINE | ID: mdl-35713261

ABSTRACT

AIM: To uncover factors that can predict the development of C5 palsy before surgery by evaluating several different parameters. MATERIAL AND METHODS: A total of 177 patients who underwent surgery between 2015 and 2020 were included in the study. In total, C5 palsy was observed in 22 (12.4%) of our patients. The radiological and clinical data of the patients were retrospectively analyzed and added to the data. RESULTS: A total of 177 patients who satisfied the criteria were included in the study, among whom 117 (66.1%) and 60 (33.9%) were male and female, respectively. Patients with ossified posterior longitudinal ligament (OPLL) (92; 52.0%) needed surgery the most. C5 palsy developed in 16/92 (17.3%) patients who had surgery for OPLL. This result was statistically significant (p < 0.001). However, a significant difference in the postoperative Pavlov ratio was noted between both groups (p=0.027). The foraminal dimensions for the C5 palsy group were significantly lower than those for the non-C5 palsy group. CONCLUSION: Smaller C5 root foramina diameter measurements were the most important predictive factor for the development of C5 palsy after open-door cervical laminoplasty. Although the pathophysiology remains to be fully understood, ischemia-reperfusion injury supposedly plays a role therein.


Subject(s)
Laminoplasty , Humans , Male , Female , Laminoplasty/adverse effects , Laminoplasty/methods , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Retrospective Studies , Paralysis/epidemiology , Paralysis/etiology , Paralysis/surgery , Radiography
14.
Turk Neurosurg ; 33(2): 296-301, 2023.
Article in English | MEDLINE | ID: mdl-36482853

ABSTRACT

AIM: To examine the effect of adiponectin administration on acute brain injury in an experimental model of cerebral ischemia/ reperfusion (I/R) in rats. MATERIAL AND METHODS: The study animals were divided into the following four groups: group I, sham (did not undergo surgical intervention and did not receive drugs); group II, the I/R model (received the intervention, but did not receive drugs); group III (I/Radiponectin) (the I/R model was used, and the animals were treated with 5 mg/kg adiponectin peritoneally 30 minutes after the ischemia); and group IV (I/R-tirofiban)( the I/R model was used, and the animals were treated with 0.5 mg/kg tirofiban peritoneally 30 minutes after the ischemia). RESULTS: Tumor necrosis factor-? (TNF-?) and interleukin (IL)-1? levels were statistically higher in the I/R group (group II) than in other groups. In the post-hoc (Tukey) test analysis, groups I, III, and IV had significantly lower TNF-? and IL-1? levels after treatment with both tirofiban and adiponectin than group II. No statistically significant difference was found between groups III and IV in terms of TNF-? levels. However, the decreased IL-1? level was more pronounced in group IV (tirofiban) than in other groups. The mean neurologic deficit scores were statistically significantly different among the groups. In the post-hoc (Tukey) test analysis, neurologic deficit scores were statistically significantly lower in groups III and IV than in group II. CONCLUSION: Adiponectin has anti-inflammatory and cerebral protective effects in experimental cerebral I/R injury.


Subject(s)
Brain Ischemia , Reperfusion Injury , Rats , Animals , Adiponectin/therapeutic use , Tirofiban/therapeutic use , Reperfusion Injury/drug therapy , Reperfusion Injury/pathology , Brain Ischemia/drug therapy , Tumor Necrosis Factor-alpha , Interleukin-1/therapeutic use , Ischemia
15.
Arch Med Sci ; 18(6): 1659-1665, 2022.
Article in English | MEDLINE | ID: mdl-36457972

ABSTRACT

Introduction: The degenerative effects of imidacloprid via oxidative stress are known. Irisin is a recently discovered peptide with energy regulator and antioxidant effects. In addition, the antioxidant potential of Vitamin D has been reported in previous studies. The current study was performed to investigate the effect of Vitamin D on testis morphology and irisin immunoreactivity in imidacloprid-treated rats. Material and methods: Thirty-two Wistar albino male rats were divided into groups: control (n = 6), corn oil (n = 6), Vitamin D (n = 6), imidacloprid (n = 7) and imidacloprid + Vitamin D (n = 7). Testis tissues were used to evaluate the histopathological, biochemical and immunohistochemical changes. Oxidative state in testis tissue was determined with total antioxidant and oxidant status markers, total antioxidant status (TAS) and total oxidant status (TOS) respectively. Results: In microscopic examination, degenerative changes in the seminiferous tubule epithelium, interstitial edema and increased irisin immunoreactivity were observed in animals given imidacloprid. Also increased TOS and decreased TAS levels were measured in these animals. It was observed that Vitamin D improved the testicular damage histopathologically when compared to the imidacloprid group. However, increase in TAS levels and decrease in both TOS levels and irisin immunoreactivity were found insignificant in animals given Vitamin D. Conclusions: In the present study it was observed that Vitamin D ameliorated testis injury caused by imidacloprid. Furthermore, imidacloprid was found to increase the immunoreactivity of irisin. In the light of our findings, we conclude that the use of Vitamin D could be beneficial against testicular damage caused by imidacloprid.

17.
Rev Assoc Med Bras (1992) ; 68(9): 1276-1281, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36228259

ABSTRACT

OBJECTIVE: Obesity, which causes many serious diseases, is increasing exponentially in childhood across the world. Epigenetic changes, as well as genetics, play an important role in the process of adipogenesis. Therefore, we aimed to examine the expression levels of obesity-related MicroRNA-130b and MicroRNA-146b and the methylation status of hypoxia factor 3A and interleukin-6 genes associated with obesity in children. METHODS: This study was performed with 98 individuals (49 obese children and 49 controls) whose DNA was isolated from peripheral blood. Gene promoter methylations were analyzed by methylation-specific Polymerase chain reaction. In addition, expression levels of MicroRNAs were determined by quantitative real-time Polymerase chain reaction in 30 children (15 obese children and 15 controls). RESULTS: Methylation status of interleukin-6 gene was 93.9% in obese children (n=46/49) and 100% (n=49/49) in control group (p>0.05). There was no methylation for hypoxia factor 3A gene (p>0.05). As a result of the study, there was no statistically significant difference in terms of methylation status for hypoxia factor 3A and interleukin-6 genes in the obese group compared to the control group. However, we found that expression levels of MicroRNA-130b (p<0.01) and MicroRNA-146b (p<0.001) were higher in the obese group. CONCLUSIONS: Results support that MicroRNA-130b and MicroRNA-146b are potential biomarkers for the prevention and early diagnosis of obesity. This is the first study on childhood obesity in the Middle Black Sea region of Turkey. We believe that the results obtained by expanding the studies in our country and neighboring countries will be more decisive.


Subject(s)
MicroRNAs , Pediatric Obesity , Child , Epigenesis, Genetic , Humans , Hypoxia/genetics , Interleukin-6/genetics , Pediatric Obesity/genetics
18.
J Coll Physicians Surg Pak ; 32(10): 1347-1349, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36205285

ABSTRACT

Extracranial metastases from primary brain tumours are mostly caused by high-grade tumours. Metastases from low-grade intracranial tumours are much rare and usually asymptomatic. We present a case of a symptomatic spinal cord compression with intradural extramedullary and diffuse leptomeningeal infiltration observed approximately 51 months after the first diagnosis of a 52-year male patient with WHO Grade 2 oligodendroglioma with temporoparietal localisation. This patient, who had the complaint of weakness in the lower extremity, was operated on due to a thoracic intradural extramedullary mass. The result of the pathological examination came out as WHO Grade 2 oligodendroglioma, and radiotherapy was planned for this seeding metastasis. The patient who experienced refractory seizures died before his radiotherapy treatment was completed. It should be kept in mind that spinal metastases may also be seen in low-grade intracranial tumours without malignant transformation as in the present case. Key Words: Spinal seeding, Spinal metastases, Low-grade oligodendroglioma.


Subject(s)
Brain Neoplasms , Oligodendroglioma , Spinal Cord Neoplasms , Spinal Neoplasms , Brain Neoplasms/pathology , Humans , Magnetic Resonance Imaging , Male , Oligodendroglioma/diagnosis , Oligodendroglioma/pathology , Oligodendroglioma/secondary , Spinal Cord Neoplasms/diagnosis , Spinal Cord Neoplasms/surgery , Spinal Neoplasms/surgery
19.
Article in English | MEDLINE | ID: mdl-35787227

ABSTRACT

BACKGROUND: Intervertebral disc degeneration (IDD) is a common and complex condition. Vascular endothelial growth factor (VEGF) is one of the key regulators of angiogenesis and vascular permeability. Nitric oxide (NO) plays a role in various physiological events. The endothelial nitric oxide synthase (eNOS) that catalyses NO generation are crucial for the regulation of NO level. This study aimed to evaluate the association between VEGF/ eNOS gene variants with IDD. MATERIALS AND METHODS: Two hundred ninety-one subjects (111 IDD patients and 180 controls) were included in the present case-control study. VEGF -2549 insertion/deletion (I/D) and eNOS VNTR variants were analysed by PCR method. The results of this analysis were evaluated for statistical significance. RESULTS: There were no statistically significant differences in genotype and allele distribution of VEGF -2549 I/D/ eNOS VNTR variants between IDD patients and control subjects. We then evaluated the association between the allele frequencies of these variants and clinical features of IDD. Lumber IDD was more common in patients carrying VEGF I/D variant D allele (p < 0.001). Also, patients with lumbar disc herniation, cervical disc herniation, lumbar stenosis, and lumbar IDD had more 4 b allele (p = 0.005, p < 0.001, p < 0.001, and p = 0.03, respectively). CONCLUSIONS: In conclusion, this study demonstrates first time that some clinical characteristics of IDD have been associated with allele frequencies of VEGF -2549 I/D/ eNOS VNTR variants.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Humans , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Displacement/genetics , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/genetics , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factors
20.
Nanomedicine ; 44: 102577, 2022 08.
Article in English | MEDLINE | ID: mdl-35716872

ABSTRACT

An efficient SERS based novel analytical approach named Cryosectioned-PDMS was developed systematically and evaluated applying on 64 thyroid biopsy samples. To utilize thyroid biopsy samples, a 20-µl volume of h-AgNPs suspension was dropped on a 5-µm thick cryosectioned biopsy specimen placed on the PDMS coated glass slide. The SERS spectra from a 10 × 10 points array acquired by mapping 22.5 µm × 22.5 µm sized area from suspended dried droplets placed on the tissue surface. The probability of correctly predicted performance for diagnosis of malignant, benign and healthy tissues was resulted in the accuracy of 100 % for the spectral bands at 667, 724, 920, 960, 1052, 1096, 1315 and 1457 cm-1 using PCA-fed LDA machine learning. The Cryosectioned-PDMS biophotonic approach with PCA-LDA predictive model demonstrated that the vibrational signatures can accurately recognize the fingerprint of cancer pathology from a healthy one with a simple and fast sample preparation methodology.


Subject(s)
Neoplasms , Spectrum Analysis, Raman , Discriminant Analysis , Humans , Neoplasms/diagnosis , Principal Component Analysis , Spectrum Analysis, Raman/methods , Thyroid Gland
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