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International Journal of Molecular... Apr 2024Energy metabolism plays a pivotal role in the pathogenesis of endometriosis. For the initial stages of the disease in adolescents, this aspect remains unexplored. The...
Energy metabolism plays a pivotal role in the pathogenesis of endometriosis. For the initial stages of the disease in adolescents, this aspect remains unexplored. The objective of this paper was to analyze the association of cellular and endosomal profiles of markers of glycolysis, mitochondrial biogenesis, apoptosis, autophagy and estrogen signaling in peritoneal endometriosis (PE) in adolescents. We included 60 girls aged 13-17 years in a case-control study: 45 with laparoscopically confirmed PE (main group) and 15 with paramesonephric cysts (comparison group). Samples of plasma and peritoneal fluid exosomes, endometrioid foci and non-affected peritoneum were tested for estrogen receptor (Erα/β), hexokinase (Hex2), pyruvate dehydrogenase kinase (PDK1), glucose transporter (Glut1), monocarboxylate transporters (MCT1 and MCT2), optic atrophy 1 (OPA1, mitochondrial fusion protein), dynamin-related protein 1 (DRP1, mitochondrial fission protein), Bax, Bcl2, Beclin1, Bnip3, P38 mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (Hif-1α), mitochondrial voltage-dependent anion channel (VDAC) and transforming growth factor (TGFβ) proteins as markers of estrogen signaling, glycolysis rates, mitochondrial biogenesis and damage, apoptosis and autophagy (Western-Blot and PCR). The analysis identified higher levels of molecules associated with proliferation (ERβ), glycolysis (MCT2, PDK1, Glut1, Hex2, TGFβ and Hif-1α), mitochondrial biogenesis (OPA1, DRP1) and autophagy (P38, Beclin1 and Bnip3) and decreased levels of apoptosis markers () in endometrioid foci compared to non-affected peritoneum and that in the comparison group ( < 0.05). Patients with PE had altered profiles of ERβ in plasma and peritoneal fluid exosomes and higher levels of Glut1, MCT2 and Bnip3 in plasma exosomes ( < 0.05). The results of the differential expression profiles indicate microenvironment modification, mitochondrial biogenesis, estrogen reception activation and glycolytic switch along with apoptosis suppression in peritoneal endometrioid foci already in adolescents.
Topics: Female; Humans; Adolescent; Endometriosis; Autophagy; Apoptosis; Glycolysis; Case-Control Studies; Organelle Biogenesis; Estrogen Receptor beta; Signal Transduction; Estrogen Receptor alpha; Biomarkers
PubMed: 38673823
DOI: 10.3390/ijms25084238 -
Journal of Clinical Medicine Apr 2024Patients with colon cancer may present at multiple different stages of the disease process. Many patients can be cured of colon cancer as a result of a simple surgical... (Review)
Review
BACKGROUND
Patients with colon cancer may present at multiple different stages of the disease process. Many patients can be cured of colon cancer as a result of a simple surgical procedure usually performed by minimally invasive techniques. However, there are a variable number of patients, estimated at approximately 10%, who have a more advanced disease. If these patients are treated by the current conventional standard of care, the likelihood for treatment failure is extremely high.
METHODS
These are not patients with known disseminated disease but patients who are at high risk of recurrent disease unless special treatments are initiated preoperatively and intraoperatively. The identification of these patients is by (1) a high-quality CT scan, (2) tumor markers found preoperatively, (3) colonoscopic findings, and (4) symptoms.
RESULTS
Patients identified as being at high risk require special preoperative treatments which include neoadjuvant chemotherapy. Intraoperative chemotherapy with HIPEC should occur as part of the treatment if peritoneal metastases are documented by biopsy. In the operating room, a thorough exploration of all possible occult peritoneal spaces for metastatic disease needs to be performed. A modified cytoreductive surgical procedure along with a colon resection is performed in order to minimize sites of occult peritoneal metastases. This includes the greater omentum, ovaries, and tubes in postmenopausal women. Peritonectomy is used to create a shroud around the tumor so that all peritoneum that has been in direct contact with the tumor surface is resected and is used as a barrier against tumor cell dissemination in the process of colon cancer resection. If peritoneal metastases are visualized at any site, HIPEC should be included as part of the treatment package.
CONCLUSIONS
I am convinced that patients at high risk of recurrence will have an improved outcome with proper preoperative evaluation, preoperative neoadjuvant chemotherapy, and a revised intraoperative management strategy.
PubMed: 38673511
DOI: 10.3390/jcm13082238 -
Foods (Basel, Switzerland) Apr 2024This study scrutinized the nutritional quality and serum biochemical indices of grass carp () cultivated in traditional pond intercropping (TPI) and in-pond raceway...
This study scrutinized the nutritional quality and serum biochemical indices of grass carp () cultivated in traditional pond intercropping (TPI) and in-pond raceway system (IPRS) aquaculture setups. The findings showed that the TPI group exhibited a superior water-holding capacity, while the IPRS showcased heightened crude lipid content and levels of textural properties such as springiness. Moreover, significant differences emerged in the fatty acid profiles, with the TPI group manifesting higher total polyunsaturated fatty acids (ΣPUFAs), EPA, DHA, and Σn-3, while the IPRS group exhibited elevated total saturated fatty acids (ΣSFAs). In terms of amino acids, valine and histidine levels were notably higher in the IPRS group, whereas lysine levels were reduced. Volatile compound analysis revealed significant variations, with the IPRS group containing more volatile substances with a better aroma, resulting in a better odor. The IPRS group performed better in serum biochemistry analysis. Additionally, grass carp in the IPRS group displayed an improved structure and greater coverage area of the visceral peritoneum, appearing lighter in color compared to the TPI group. TPI mainly influences nutritional elements; IPRSs primarily affect muscle texture, serum biochemistry, and overall health. This study aims to fill the gap in quality comparison research and provide an important scientific basis.
PubMed: 38672919
DOI: 10.3390/foods13081248 -
Iranian Journal of Kidney Diseases Mar 2024Peritoneal dialysis (PD) is an effective treatment modality for advanced kidney failure, offering patients a significant degree of independence. However, the...
Correlation Between the 8-hydroxy-2'-deoxyguanosine Level in the Peritoneal Solution of Patients Undergoing Peritoneal Dialysis and the Peritoneal Equilibration Test, Kt/V, Ferritin, and Albumin Levels.
INTRODUCTION
Peritoneal dialysis (PD) is an effective treatment modality for advanced kidney failure, offering patients a significant degree of independence. However, the long-term use of PD is limited due to the degeneration of the peritoneal membrane, resulting in reduced dialysis adequacy. Evaluating the peritoneal membrane condition in patients with advanced kidney failure who are undergoing PD is challenging with existing methods. Therefore, this study aimed to investigate the correlation between 8-hydroxy-2'-deoxyguanosine (8OHDG) levels in the peritoneal solution of patients undergoing PD and various factors, such as peritoneal equilibration test (PET), dialysis adequacy (Kt/V), underlying diseases, serum ferritin, and albumin levels. 8OHDG is a sensitive marker of oxidative stress caused by DNA damage.
METHODS
A total of 56 patients were included in this cross-sectional study. Five milliliters of PD fluid were collected from the patients, and 8-OHdG levels were measured using ELISA method. Then, they were compared with PET, Kt/V, albumin, and ferritin markers in the patients' files, and the results were analyzed by statistical tests.
RESULTS
The study examined the correlation between 8OHDG and other markers. It was found that this index had significant associations with PET and underlying HTN (P < .05), whereas no significant associations were identified with the other markers.
CONCLUSION
The results of the present study demonstrate that the level of 8OHDG, as one of the oxidative stress markers, could be used to evaluate the function of the peritoneum in patients undergoing PD. DOI: 10.52547/ijkd.7654.
Topics: Female; Humans; Male; 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cross-Sectional Studies; Deoxyguanosine; Ferritins; Kidney Failure, Chronic; Oxidative Stress; Peritoneal Dialysis; Peritoneum; Serum Albumin
PubMed: 38660699
DOI: 10.5254/fte08z03 -
International Journal of Antimicrobial... Jul 2024The aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, the potential of apramycin...
BACKGROUND
The aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, the potential of apramycin in the treatment of drug-resistant bloodstream infections (BSIs) has not yet been assessed.
METHODS
The resistance gene annotations of 40 888 blood-culture isolates were analysed. In vitro profiling of apramycin comprised cell-free translation assays, broth microdilution, and frequency of resistance determination. The efficacy of apramycin was studied in a mouse peritonitis model for a total of nine Escherichia coli and Klebsiella pneumoniae isolates.
RESULTS
Genotypic aminoglycoside resistance was identified in 87.8% of all 6973 carbapenem-resistant Enterobacterales blood-culture isolates, colistin resistance was shown in 46.4% and apramycin in 2.1%. Apramycin activity against methylated ribosomes was > 100-fold higher than that for other aminoglycosides. Frequencies of resistance were < 10 at 8 × minimum inhibitory concentration (MIC). Tentative epidemiological cut-offs (TECOFFs) were determined as 8 µg/mL for E. coli and 4 µg/mL for K. pneumoniae. A single dose of 5 to 13 mg/kg resulted in a 1-log colony-forming unit (CFU) reduction in the blood and peritoneum. Two doses of 80 mg/kg resulted in an exposure that resembles the AUC observed for a single 30 mg/kg dose in humans and led to complete eradication of carbapenem- and aminoglycoside-resistant bacteraemia.
CONCLUSION
Encouraging coverage and potent in vivo efficacy against a selection of highly drug-resistant Enterobacterales isolates in the mouse peritonitis model warrants the conduct of clinical studies to validate apramycin as a drug candidate for the prophylaxis and treatment of BSI.
Topics: Animals; Klebsiella pneumoniae; Nebramycin; Anti-Bacterial Agents; Escherichia coli; Microbial Sensitivity Tests; Mice; Disease Models, Animal; Carbapenems; Aminoglycosides; Klebsiella Infections; Peritonitis; Escherichia coli Infections; Bacteremia; Humans; Female; Carbapenem-Resistant Enterobacteriaceae; Drug Resistance, Bacterial
PubMed: 38653351
DOI: 10.1016/j.ijantimicag.2024.107181 -
Acta Oncologica (Stockholm, Sweden) Apr 2024The chronic, inflammatory skin disease hidradenitis suppurativa (HS) (prevalence: 0.5%-1%, diagnostic delay: 7-10 years) primarily arises in younger adults and...
BACKGROUND
The chronic, inflammatory skin disease hidradenitis suppurativa (HS) (prevalence: 0.5%-1%, diagnostic delay: 7-10 years) primarily arises in younger adults and frequently coincides with autoimmune comorbidities and unhealthy life-styles (smoking and obesity). These factors are known to increase cancer risk, but despite this, information on cancer occurrence among HS patients is scarce.
MATERIALS AND METHODS
A nationwide retrospective register-based study assessing relative risk of cancer - overall and by anatomical site - following HS diagnosis expressed as standardized incidence ratios (SIRs), which is ratios between observed cases among all Danes diagnosed with HS since 1977 and expected cases based on cancer incidence rates of the entire Danish population during the same period.
RESULTS
Participants consisted of a cohort of 13,919 Danes with HS, who during an average of 14.2 years of follow-up developed a total of 1,193 incident cancers, corresponding to a 40% increased risk (SIR = 1.4, 95% CI: 1.3 to 1.4, p < 0.001). Increased risks were observed for cancers of the respiratory system, oral cavity and pharynx, digestive organs and peritoneum, urinary tract, and the lymphatic tissues.
INTERPRETATION
These findings underline an unmet need for health monitoring, lifestyle interventions and cancer screening if and when relevant.
Topics: Humans; Hidradenitis Suppurativa; Denmark; Male; Incidence; Neoplasms; Registries; Female; Adult; Middle Aged; Retrospective Studies; Young Adult; Aged; Adolescent; Risk Factors
PubMed: 38647025
DOI: 10.2340/1651-226X.2024.26182 -
Theranostics 2024A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured...
Lipid nanoparticle encapsulated large peritoneal macrophages migrate to the lungs via the systemic circulation in a model of clodronate-mediated lung-resident macrophage depletion.
A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured tissues and impart wound healing properties. Here, we sought to expand on this unique ability of large peritoneal macrophages (LPMs) by investigating whether these GATA6+ LPMs could also intravasate into systemic circulation and migrate to extra-peritoneally located lungs upon ablating lung-resident alveolar macrophages (AMs) by intranasally administered clodronate liposomes in mice. C12-200 cationic lipidoid-based nanoparticles were employed to selectively deliver a small interfering RNA (siRNA)-targeting CD-45 labeled with a cyanine 5.5 (Cy5.5) dye to LPMs via intraperitoneal injection. We utilized a non-invasive optical technique called Diffuse Flow Cytometry (DiFC) to then systemically track these LPMs in real time and paired it with more conventional techniques like flow cytometry and immunocytochemistry to initially confirm uptake of C12-200 encapsulated siRNA-Cy5.5 (siRNA-Cy5.5 (C12-200)) into LPMs, and further track them from the peritoneal cavity to the lungs in a mouse model of AM depletion incited by intranasally administered clodronate liposomes. Also, we stained for LPM-specific marker zinc-finger transcription factor GATA6 in harvested cells from biofluids like broncho-alveolar lavage as well as whole blood to probe for Cy5.5-labeled LPMs in the lungs as well as in systemic circulation. siRNA-Cy5.5 (C12-200) was robustly taken up by LPMs. Upon depletion of lung-resident AMs, these siRNA-Cy5.5 (C12-200) labeled LPMs rapidly migrated to the lungs via systemic circulation within 12-24 h. DiFC results showed that these LPMs intravasated from the peritoneal cavity and utilized a systemic route of migration. Moreover, immunocytochemical staining of zinc-finger transcription factor GATA6 further confirmed results from DiFC and flow cytometry, confirming the presence of siRNA-Cy5.5 (C12-200)-labeled LPMs in the peritoneum, whole blood and BALF only upon clodronate-administration. Our results indicate for the very first time that selective tropism, migration, and infiltration of LPMs into extra-peritoneally located lungs was dependent on clodronate-mediated AM depletion. These results further open the possibility of therapeutically utilizing LPMs as delivery vehicles to carry nanoparticle-encapsulated oligonucleotide modalities to potentially address inflammatory diseases, infectious diseases and even cancer.
Topics: Animals; Clodronic Acid; Nanoparticles; Mice; Lung; Macrophages, Peritoneal; Macrophages, Alveolar; RNA, Small Interfering; GATA6 Transcription Factor; Liposomes; Mice, Inbred C57BL; Carbocyanines; Cell Movement; Flow Cytometry
PubMed: 38646640
DOI: 10.7150/thno.91062 -
Gynecologic Oncology Reports Jun 2024Given the high risk of complications associated with cesarean hysterectomy for placenta accreta spectrum (PAS), any surgical approach and technique can yield utility in...
Given the high risk of complications associated with cesarean hysterectomy for placenta accreta spectrum (PAS), any surgical approach and technique can yield utility in reducing the surgical morbidity. Here, we propose the 3-2-1 approach as a schema to be implemented in the proper setting for the surgical management of a PAS cesarean hysterectomy. The 3-2-1 approach begins with the surgical dissection of three anatomical landmarks that ultimately facilitate a safe surgical site for the ligation and transection of the uterine vessels. First-step is identification of the three anatomical landmarks which are posterior lower uterine segment peritoneum de-serosalization, identification of the ureters laterally, and anterior bladder dissection. Posterior-to-anterior progression avoids encountering dense adhesions and hypervascularity in the anterior lower uterine segment early in the surgery. Further, allows better mobilization of the uterus to identify the anatomical landmarks laterally and anteriorly. Second-step is to deploy the 2-hand technique where the surgeon places one hand anteriorly and the other hand posteriorly in the lower uterine segment below the placental bed. The surgeon brings both hands together with flexed fingers perpendicular to the uterine tissue and gently elevates the uterus and placenta out of the pelvis and ensures safe anatomical distance to surrounding structures. Third-step is the consideration of a supracervical hysterectomy. In summary, this 3-2-1 approach to reflect the anatomy of enlarged lower uterine segment in PAS is a stepwise schema that can aid surgeons in the completion of a cesarean hysterectomy, with the goal to improve surgical outcomes.
PubMed: 38646446
DOI: 10.1016/j.gore.2024.101366 -
Cureus Mar 2024Background Colorectal cancer constitutes a significant public health challenge, despite remarkable strides made in the last two decades, particularly in the medical...
Background Colorectal cancer constitutes a significant public health challenge, despite remarkable strides made in the last two decades, particularly in the medical management of metastatic stages. Notable progress has been achieved through targeted therapies such as anti-epidermal growth factor receptors or anti-angiogenic antibodies, as well as advancements in surgical approaches for hepatic metastases. This study seeks to assess the efficacy and safety of bevacizumab plus chemotherapy in individuals with metastatic colorectal cancer. Methodology This is an observational, cross-sectional, retrospective study of all patients who were followed up for metastatic colorectal cancer with unresectable metastases and were treated with bevacizumab in combination with standard chemotherapy from January 2010 until December 2019 in the medical oncology department of the Centre Hospitalier Universitaire (CHU) Souss-Massa of Agadir. Results Of the total 162 cases, 117 (72%) had metastatic disease, and 45 (28%) progressed to metastatic disease after initial treatment. The median age of the patients was 55 years (range = 23-79 years) with a sex ratio of 1.1 (M/F). The tumor was located in the left colon in 135 (83.3%) patients. The results represented adenocarcinoma in 137 (84.6) cases and mucinous subtype in 23 (14.19) cases. The three most common sites of metastasis were the liver (99, 61.1), peritoneum (67, 41.3), and lung (33, 20.3). In the first line, all patients received bi-chemotherapy plus bevacizumab, i.e., fluorouracil, oxaliplatin, and leucovorin in 34 (20.9%) patients; capecitabine plus oxaliplatin in 88 (54.3%) patients; leucovorin, fluorouracil, and irinotecan in 17 (10.4%) patients; and capecitabine plus irinotecan in 23 (14.1%) patients. Response after first-line treatment was progression in 74 (45.7) cases, stability in 42 (25.9) cases, partial response in 35 (21.6) cases, and complete response in 11 (6.8) cases. Nine (6%) patients were able to benefit from surgical resection of metastatic lesions. Overall, 77 (47%) patients received second-line chemotherapy, i.e., 5-FU with irinotecan in 40 (51.8%) cases or with oxaliplatin in 30 (38.8%) cases. Two patients developed undesirable side effects under bevacizumab (hypertension). The median progression-free survival and median overall survival of the study cohort were 9 months and 14 months, respectively. Nevertheless, patients who underwent primary tumor resection (p = 0.048), those with right‑sided tumors (p = 0.022), those who received a higher number of treatment cycles (p = 0.020), and those who received maintenance treatment (p = 0.001) had a longer median overall survival. Conclusions Chemotherapy combination with bevacizumab is considered as the cornerstone of metastatic colorectal cancer treatment in our region. With the new healthcare and social security systems, easier access to expensive treatments and molecular pathology tests is currently available. It is important to highlight that real-world data can offer valuable insights into the daily clinical practice of medical oncology.
PubMed: 38646225
DOI: 10.7759/cureus.56733