Targeting apoptosis and unfolded protein response: the impact of ß-hydroxybutyrate in clear cell renal cell carcinoma under glucose-deprived conditions.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) plays a significant role in the mortality associated with kidney cancer. Targeting biological processes that inhibit cancer growth opens up new treatment possibilities. The unfolded protein response (UPR) and apoptosis have crucial roles in RCC progression. This study investigates the impact of ß-hydroxybutyrate (BHB) on ccRCC cells under glucose deprivation resembling as a ketogenic diet. METHOD: Caki-1 ccRCC cells were exposed to decreasing glucose concentrations alone or in combination with 10 or 25 mM BHB during 48 and 72 h. Cell viability was determined using MTT assay. The mRNA expression level of apoptosis-and UPR-related markers (Bcl-2, Bax, caspase 3, XBP1s, BIP, CHOP, ATF4, and ATF6) were assayed by qRT-PCR. RESULTS: Cell viability experiments demonstrated that combining different doses of BHB with decreasing glucose levels initially improved cell viability after 48 h. Nevertheless, this trend reversed after 72 h, with higher impacts disclosed at 25 mM BHB. Apoptosis was induced in BHB-treated cells as caspase-3 and Bax were increased and Bcl-2 was downregulated. BHB supplementation reduced UPR-related gene expression (XBP1s, BIP, CHOP, ATF4, and ATF6), revealing a possible mechanism by which BHB affects cell survival. CONCLUSION: This research emphasizes the dual effect of BHB, initially suppressing cell- survival under glucose deprivation but eventually triggering apoptosis and suppressing UPR signaling. These data highlight the intricate connection between metabolic reprogramming and cellular stress response in ccRCC. Further research is recommended to explore the potential of BHB as a therapeutic strategy for managing ccRCC.

The diagnostic values of procalcitonin and interleukin 6 in acute appendicitis.

OBJECTIVE: Despite the recent use of computed tomography scan and diagnostic laparoscopy, acute appendicitis is still highly misdiagnosed. Timely diagnosis of acute appendicitis is more crucial in children and elderly patients because of vague symptoms and rapid progression to perforation in these age groups, which may result in high rates of morbidity and mortality. The aim of the present study was to find the diagnostic values of procalcitonin and interleukin 6 (IL-6) for diagnosing acute appendicitis in our center. MATERIAL AND METHODS: Patients who were suspected of acute appendicitis and who were referred to the emergency department of a tertiary care urban hospital in 2016 were enrolled in the study. A 5 mL blood sample was obtained from each patient before appendectomy and was examined for procalcitonin and IL-6. Then, the resected specimen of the appendix was studied by a pathologist, and a definite diagnosis was made. RESULTS: Eighty patients including 53 (66.3%) men who underwent appendectomy were enrolled in the study. The diagnosis of acute appendicitis was histopathologically confirmed in 60 (75%) patients including 18, 20, and 22 patients with inflammatory, suppurative, and gangrenous/perforated appendicitis, respectively. The sensitivity and specificity of procalcitonin versus IL-6 for diagnosing acute appendicitis were 65% and 80% vs. 76% and 55%, respectively. The sensitivity and specificity of concurrent procalcitonin and IL-6 for diagnosing acute appendicitis were 95% and 55%, respectively. CONCLUSION: Our study suggests that parallel measurement of procalcitonin and IL-6 decreases unnecessary negative appendectomies.

Laparoscopic In Situ Dismembered Pyeloplasty Can Facilitate Laparoscopic Ureteropelvic Junction Obstruction Repair: A Prospective Cohort Trial.

PURPOSE: To describe the technique of laparoscopic in situ dismembered pyeloplasty as a modified technique during which the alignment of ureter and renal pelvis remains intact during ureteropelvic junction (UPJ) anastomosis. We also assessed intraoperative and postoperative outcomes of this modification in comparison to standard laparoscopic dismembered pyeloplasty. PATIENTS AND METHODS: Patients with significant primary UPJ obstruction without any history of abdominal surgery, high ureter insertion, or renal anomalies were considered. The patients were consecutively enrolled one after another into one of two study groups: classic laparoscopic dismembered pyeloplasty (Group I) or laparoscopic in situ dismembered pyeloplasty (Group II), however, those with aberrant vessels crossing the UPJ were allocated specifically to Group I because UPJ anastomosis should be done anterior to the aberrant vessels. Demographic data, intraoperative timings, and postoperative and follow-up outcomes were compared in the two groups. RESULTS: Patients in Group I (n = 23) and Group II (n = 14) had similar demographic characteristics. Mean operative time was significantly longer in Group I (103.8 ± 19.95 minutes vs 89.5 ± 18.90 minutes, p = 0.038). Total duration of UPJ repair and anastomosis was also significantly longer in Group I (92.7 ± 15.82 minutes vs 78.4 ± 14.76 minutes, p = 0.021). The method of pyeloplasty significantly affected the time required to prepare ureter and renal pelvis (p = 0.017) and the duration of UPJ anastomosis (p = 0.014). Both were shorter in Group II. Mean follow-up period was 14.4 ± 7.42 months in Group I and 14.05 ± 7.93 months in Group II (p = 0.88). Success rate was 95.6% in Group I and 100% in Group II (p = 0.42). CONCLUSION: Laparoscopic in situ pyeloplasty is a safe and effective approach that can help simplify laparoscopic pyeloplasty, especially at teaching centers where surgeons with variable levels of experience perform laparoscopic procedures.

First report of c. 1499G>C mutation in a 6-month-child with cystic fibrosis.

So far, more than 1800 mutations identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this case report, we presented first report of c. 1499G>C mutation in a 6-month-old girl with cystic fibrosis (CF) diagnosis. A 6-month-old girl with weakness and meconium Ileus referred to the pediatric clinic in Ilam, in the west of Iran. Patient's skin was dark and suffered from bronchiectasis. The sweat test was performed, and the concentration of chloride and sodium in patient's sweat was 130-135 mmol/L and 125-128 mmol/L, respectively. The exon 10 mutation analysis of a CF patient was performed. CFTR mutation analysis revealed the identification of 2 mutations in patient, the mutations were p.F508del (ΔF508) and c. 1499G>C (cd500), respectively. The mutation c. 1499G>C (cd500) were found for the first time in the world. Assessing this mutation in future study and genetic investigation is recommended.

Congenital epulis in the newborn, review of the literature and a case report.

Congenital epulis (CE) is a rare tumor of the newborn, also known as granular cell tumor or congenital gingival granular cell tumor because of its histologic features. Neumann first described CE in 1871. Epulis is seen only in the newborn and is a different entity from other granular cell tumors. CE has a female predilection with 8:1 ratio. Epulis is most frequently located on the anterior maxillary alveolar ridge and usually occurs as a single mass although 10% cases occur as multiple. CE clinically appears as a pedunculated protuberant mass, which may interfere with respiration or feeding. In cases with large lesions mechanical oral and nasal obstruction can impair fetal deglutition and neonatal respiratory efforts resulting in polyhydramnios prenatally or respiratory impairment postnatally. The exact histiogenesis is still uncertain. The recommended treatment is prompt surgical resection. Recurrences of the tumor and damage to future dentition have not been reported. Spontaneous regression of congenital epulis has been reported in a few cases. However, surgical excision is generally indicated due to interference with feeding or respiration. We report a female neonate with congenital multiple tumors in the anterior maxillary alveolar ridge and review the relevant literature. The tumors were resected by surgical excision. The intraoperative and postoperative course was uneventful. Follow-up for 6 months did not show recurrence.