Nicotinamide phosphoribose transferase facilitates macrophage-mediated pulmonary fibrosis through the Sirt1-Smad7 pathway in mice.

Pulmonary fibrosis is a challenging lung disease characterized by a bleak prognosis. A pivotal element in the progression of this disease is the dysregulated recruitment of macrophages. Nicotinamide phosphoribose transferase (NAMPT), secreted by alveolar epithelial cells and inflammatory cells, has been previously identified to influence macrophage inflammation in acute lung injury through the nicotinamide adenine dinucleotide (NAD) rescue synthesis pathway. Nonetheless, the exact role of NAMPT in the regulation of lung fibrosis is yet to be elucidated. In our research, we employed bleomycin (BLM) to induce pulmonary fibrosis in Namptflox/flox;Cx3cr1CreER mice, using Namptflox/flox mice as controls. Our findings revealed an augmented expression of NAMPT concurrent with a marked increase in the secretion of NAD and inflammatory cytokines such as IL-6, TNF-α, and TGF-ß1 post-BLM treatment. Furthermore, an upsurge in NAMPT-positive macrophages was observed in the lungs of BLM-treated Namptflox/flox mice. Notably, a conditional knockout of NAMPT (NAMPT cKO) in lung macrophages curtailed the BLM-induced inflammatory responses and significantly mitigated pulmonary fibrosis. This was associated with diminished phospho-Sirt1 (p-Sirt1) expression levels and a concomitant rise in mothers against decapentaplegic homolog 7 (Smad7) expression in BLM-treated mouse lungs and murine RAW 264.7 macrophage cells. Collectively, our data suggests that NAMPT exacerbates macrophage-driven inflammation and pulmonary fibrosis via the Sirt1-Smad7 pathway, positioning NAMPT as a promising therapeutic target for pulmonary fibrosis intervention.

Quantitative comparison of three thyroidectomy approaches in neck muscles, voice, and swallowing functions.

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.

Clinical application of superselective transarterial embolization of renal tumors in zero ischaemia robotic-assisted laparoscopic partial nephrectomy.

Objective: To assess the feasibility and safety of zero ischaemia robotic-assisted laparoscopic partial nephrectomy (RALPN) after preoperative superselective transarterial embolization (STE) of T1 renal cancer. Methods: We retrospectively analyzed the data of 32 patients who underwent zero ischaemia RALPN after STE and 140 patients who received standard robot-assisted laparoscopic partial nephrectomy (S-RALPN). In addition, we selected 35 patients treated with off-clamp RALPN (O-RALPN) from September 2017 to March 2022 for comparison. STE was performed by the same interventional practitioner, and zero ischaemia laparoscopic partial nephrectomy (LPN) was carried out by experienced surgeon 1-12 hours after STE. The intraoperative data and postoperative complications were recorded. The postoperative renal function, routine urine test, urinary Computed Tomography (CT), and preoperative and postoperative glomerular filtration rate (GFR) data were analyzed. Results: All operations were completed successfully. There were no cases of conversion to opening and no deaths. The renal arterial trunk was not blocked. No blood transfusions were needed. The mean operation time was 91.5 ± 34.28 minutes. The mean blood loss was 58.59 ± 54.11 ml. No recurrence or metastasis occurred. Conclusion: For patients with renal tumors, STE of renal tumors in zero ischaemia RALPN can preserve more renal function, and it provides a safe and feasible surgical method.

Application of anatomic reconstruction technique for periurethral structure in robotic assisted laparoscopic radical prostatectomy.

Objective: To investigate the outcome of patients underwent anatomic periurethral reconstruction during robotic assisted laparoscopic radical prostatectomy (RARP). Materials and methods: During August 2016 to May 2018, periurethral structure anatomic reconstruction was performed during RARP in 58 consecutive patients. The control group consists of another 50 patients had no reconstruction procedure during RARP. Perioperative data of these patients were collected retrospectively, including operation time, anastomosis time, intraoperative blood loss, duration of indwelling catheter, length of hospital stay, complications, postoperative pathology, and continence outcome at 1,3,6 and 12 months. Results: All cases were successfully performed without conversion to open or laparoscopic surgery. There were no major intraoperative or postoperative complications.The percentage of patients maintain continence in the reconstruction group versus non-reconstruction group: At 1 month 84.5% (49/58)versus 70.0% (35/50), at 3 months 89.7% (52/58)versus 78.0% (39/50), at 6 months 91.3% (53/58)versus 86.0% (43/50) and 1 year after surgery 100.0% (58/58)versus 96.0% (48/50). Reconstruction group showed better continence outcome in 1 and 3 months (P<0.05). There is no statistical differences in 6 month and 1 year. Conclusion: Anatomic reconstruction of periurethral structure during RARP is safe and feasible with reduced duration of indwelling catheter and better continence outcome.

Association of visceral and subcutaneous fat with bone mineral density in US adults: a cross-sectional study.

The relationship between the accumulation of fat in visceral or subcutaneous tissue and bone mineral density (BMD) remains unclear. Our primary objective in this study was to illuminate this relationship by conducting an investigation on a vast scale, encompassing a nationally representative population in the United States. A weighted multiple linear regression model was established to evaluate the relationship between visceral fat, subcutaneous fat, and BMD. Additionally, the exploration of the potential nonlinear relationship was conducted employing the methodology of smooth curve fitting. In order to determine potential inflection points, a two-stage linear regression model was utilized. A total of 10,455 participants between the ages of 20 and 59 were included in this study. Various weighted multiple linear regression models revealed a negative correlation between lumbar BMD and visceral mass index (VMI) and subcutaneous mass index (SMI). However, the association between VMI and lumbar BMD displayed a U-shaped pattern upon employing the smooth curve fitting, and the inflection point of 0.304 kg/m2was determined using a two-stage linear regression model. Our findings indicated a negative association between subcutaneous fat and BMD. A U-shaped relationship was observed between visceral fat and BMD.

The incidence trends of oral cancers worldwide from 1988 to 2012 and the prediction up to 2030.

BACKGROUND: This paper aims to analyze the time trend of OCs incidence in 43 countries (1988-2012) and predict the incidence trend of OCs (2012-2030). METHODS: In the database for Cancer Incidence in Five Continents, the annual data on OCs incidence grouped by age and gender were obtained from 108 cancer registries in 43 countries. The age-standardized incidence rates were calculated, and the Bayesian age-period-cohort model was used to predict the incidence in 2030. RESULTS: South Asia and Oceania had the highest ASR in 1988 (9.24/100 000) and 2012 (6.74/100 000). It was predicted that India, Thailand, the United Kingdom, the Czech Republic, Austria, and Japan would be the countries with an increased incidence of OCs in 2030. CONCLUSION: Regional custom is an important factor affecting the incidence of OCs. According to our predictions., it is necessary to control risk factors according to local conditions and enhance screening and education.

Clinical application of endoscopic surgery using a gasless unilateral transaxillary approach in the treatment of primary hyperparathyroidism.

Objectives: To investigate the safety and feasibility of gasless axillary parathyroid surgery in the treatment of primary hyperparathyroidism. Methods: A total of 12 patients who received gasless axillary parathyroidectomy (endoscope group) and 14 patients who received traditional open parathyroidectomy (open group) from January 2019 to April 2022 were screened and included. The differences in baseline characteristics, surgical efficiency, incidence rate of complications, changes in biochemical indicators, and incision satisfaction between the two groups were analyzed and compared. Results: The proportion of young patients was higher in the endoscopic group than in the open group, and the difference was statistically significant [(41.33 ± 13.65) years vs. (58.00 ± 9.44) years, P < 0.01]. The differences in operation time, intra-operative blood loss, post-operative drainage volume, hospital stay, and surgical efficiency between the two groups yielded no statistical significance (P > 0.05). Patients in the open group had more significant neck pain 3 days after surgery (P = 0.046), but the degree of pain 3 months after surgery was the same in the 2 groups (P = 0.432). Evaluation of post-operative mature stage scar and incision satisfaction regarding aesthetics in the endoscope group were significantly superior to that in the open group [(1.92 ± 0.92) points vs. (0.92 ± 1.00) points, P = 0.017 and (1.57 ± 0.51) points vs. (1.00 ± 0.013) points, P = 0.013, respectively]. No statistical significance was found in terms of incidence rate of post-operative fever (P > 0.05). No temporary recurrent laryngeal nerve injury, post-operative bleeding, incision hematoma infection, or other complications were observed. Comparing the two groups, the extent of the level decrease of PTH was similar to that of serum calcium and phosphorus (P < 0.05), where most patients experienced transient hypocalcemia after operation yielding no significant difference in incidence (P = 0.225). During a follow-up period of 3 to 36 months, a total of 1 patient in the open group experienced recurrence at 10 months after surgery and was treated non-surgically. Conclusion: Gasless axillary approach to parathyroid surgery for primary hyperparathyroidism possesses good safety and patient satisfaction in terms of aesthetics.

Case report: Successful treatment of a rare case of combined parathyroid adenoma, cervical bronchogenic cyst, and tracheal diverticulum with gasless endoscopic resection of neck masses via an axillary approach: A case report and literature review.

Parathyroid adenoma (PA), one of the most common causes of hyperparathyroidism, generally involves a single parathyroid gland and is manifested as hyperparathyroidism. Bronchogenic cysts are rare congenital cystic lesions caused by a development malformation in bronchi during the embryonic period, which mostly occur in the lung and mediastinum, with an extremely low morbidity rate in the neck. A 27-year-old young female was found to suffer from hyperparathyroidism on routine physical examination, and further examination suggested a cystic lesion in the right inferior parathyroid area combined with a tracheal diverticulum. Therefore, she was initially diagnosed with cystic hyperplasia of the parathyroid glands complicated by a tracheal diverticulum. Gasless endoscopic resection of neck masses via an axillary approach was performed because of the high requirements for the surgical cosmetic effect of the patient. During the surgery, we observed that the preoperatively diagnosed cystic lesion was a combination of two masses, which were successfully resected under endoscopy. Based on the postoperative pathology and clinical features, the patient was eventually diagnosed with a rare case of triple diseases including PA, cervical bronchial cyst, and tracheal diverticulum. Now, the patient recovered well as per the follow-up with no signs of recurrence and was extremely satisfied with the cosmetic effect of the surgery.

Perchlorotrityl radical-fluorophore conjugates as dual fluorescence and EPR probes for superoxide radical anion.

Perchlorotrityl radicals, mono-substituted with a fluorophore using an amide linker of varying chain length, were synthesized and characterized. Electron paramagnetic resonance (EPR) spectroscopic study indicated free-electron coupling with the aromatic hydrogen nuclei and long-range coupling with the methylene hydrogens of the linker group. Reactivity of the fluorophore-conjugated trityls with superoxide radical anion showed quenching of EPR signal and enhancement of fluorescence emission spectrum. This work presents the first example of a perchlorotrityl-fluorophore conjugate that can potentially be employed as a dual probe for the detection of superoxide under oxidative stress-mediated conditions in biological systems.

A facile microfluidic method for production of liposomes.

BACKGROUND: Ethanol injection is widely used in liposome preparation. However, the parameters determining particle size distribution of the liposomal preparation has not been fully defined. MATERIALS AND METHODS: A syringe pump-driven microfluidic injection device was used to produce liposomes under different conditions. RESULTS: Particle size of the liposomes was decreased with decrease in needle diameter (or increase in hydrodynamic pressure), decrease in lipid concentration in the alcohol solution, decrease in phase transition temperature (T(m)) of the lipid bilayer and the absence of cholesterol (or decrease in, membrane rigidity). CONCLUSION: The device used is simple to adopt and can be used for affordable production of liposomes with tunable particle size.

4-Aryl-1,3,2-oxathiazolylium-5-olate: a novel GST inhibitor to release JNK and activate c-Jun for cancer therapy.

PURPOSE: The over-expression of glutathion S-transferase Pi (GSTpi) in tumors and inhibitory effect of GSTpi to JNK are two possible causes of the development of drug-resistance in chemotherapy. This research is to develop a novel pH-controlled NO donor to inhibit GSTpi(and to activate the JNK/c-Jun pathway (omit "to induce apoptosis"). METHODS: Four 4-Aryl-1,3,2-oxathiazolylium-5-olate (OZO) derivatives with varying aryl para-substitutions (-H, -CF(3), -Cl, and -OCH(3)) were synthesized. Anticancer activity was determined by MTS assay. GST activity was measured with spectrophotometry using 1-chlro-2,4-dinitrobenzene (CDNB) and GSH as substrates. (omit "Apoptosis was evaluated by annexin V staining and flow cytometry"). c-Jun N-terminal kinase 1 (JNK1) association with GSTpi and activation of c-Jun were evaluated with immunoprecipitation and western blot. RESULTS: OZO derivatives showed anticancer effect against leukemia and breast cancer cells by MTS assay. The relative potency of their anticancer effects is OZO-H > OZO-Cl, OZO-OMe > OZO-CF(3). The anticancer activity of these compounds was correlated with their inhibition of GST activity in cancer cells. The immunoprecipitation result showed that the treatment of OZO-H released JNK1 from GSTpi-JNK1 complex. Consequently, the treatment of OZO-H in cancer cells induced JNK1 phophorylation and activated c-Jun in cancer cells. CONCLUSION: OZO-H is a novel GST inhibitor to release JNK1 for activation of JNK/c-Jun pathway (original is "c-Jun to trigger apoptosis in cancer cells"). It provides a new class of GST target compound for anticancer therapy.

4-Aryl-1,3,2-oxathiazolylium-5-olates as pH-controlled NO-donors: the next generation of S-nitrosothiols.

S-Nitrosothiols (RSNOs) are important exogenous and endogenous sources of nitric oxide (NO) in biological systems. A series of 4-aryl-1,3,2-oxathiazolylium-5-olates derivatives with varying aryl para-substituents (-CF3, -H, -Cl, and -OCH3) were synthesized. These compounds were found to release NO under acidic condition (pH = 5). The decomposition pathway of the aryloxathiazolyliumolates proceeded via an acid-catalyzed ring-opening mechanism after which NO was released and an S-centered radical was generated. Electron paramagnetic resonance (EPR) spin trapping studies were performed to detect NO and the S-centered radical using the spin traps of iron(II) N-methyl-D-glucamine dithiocarbamate [(MGD)2-FeII] and 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Also, EPR spin trapping and UV-vis spectrophotometry were used to analyze the effect of aryl para substitution on the NO-releasing property of aryloxathiazolyliumolates. The results showed that the presence of an electron-withdrawing substituent such as -CF3 enhanced the NO-releasing capability of the aryloxathiazolyliumolates, whereas an electron-donating substituent like methoxy (-OCH3) diminished it. Computational studies using density functional theory (DFT) at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level were used to rationalize the experimental observations. The aryloxathiazolyliumolates diminished susceptibility to reduction by ascorbate or gluthathione, and their capacity to cause vasodilation as compared to other S-nitrosothiols suggests potential application in biological systems.

N-hydroxyguanidines as substrates of nitric oxide synthases.

Nitric oxide (NO) has been implicated in a wide variety of disease states. Both inhibitors and substrates of nitric oxide synthase (NOS) could have great therapeutic potential in the treatment of these diseases. There is considerable pharmacological interest in developing inhibitors of NOS, and hundreds of inhibitors have been identified. In contrast, the study on NOS substrates is less active. The advances in the identification, design and development of NOS substrates are discussed in this review. The focus is the chemistry and biochemistry of N-hydroxyguanidines. The crystal structures of substrates bound to NOSs and the mechanisms of NOS catalyzed NO generation from substrates are also discussed.

New glycosidase activated nitric oxide donors: glycose and 3-morphorlinosydnonimine conjugates.

[reaction: see text] To achieve site specific delivery of nitric oxide (NO), a new class of glycosidase activated NO donors has been developed. Glucose, galactose, and N-acetylneuraminic acid were covalently coupled to 3-morphorlinosydnonimine (SIN-1), a mesoionic heterocyclic NO donor, via a carbamate linkage at the anomeric position. The beta-glycosides were successfully prepared for these conjugates, while the alpha-glycosidic compounds were very unstable. The new stable sugar-NO conjugates could release NO in the presence of glycosidases. Such NO prodrugs may be used as enzyme activated NO donors in biomedical research.

Sialated diazeniumdiolate: a new sialidase-activated nitric oxide donor.

A new sialated diazeniumdiolate has been synthesized, and the glycosylation product was exclusively an alpha anomer. This new nitric oxide donor exhibited significantly improved stability as compared to its parent diazeniumdiolate salts, and it could be efficiently hydrolyzed by neuraminidase to release nitric oxide with a K(m) of 0.14 mM. The sialic acid-NO conjugate would be a valuable prodrug that targets NO to influenza viruses.