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Neuropharmacology Jul 2024Postnatal hippocampal neurogenesis is essential for learning and memory. Hippocampal neural precursor cells (NPCs) can be induced to proliferate and differentiate into...
Postnatal hippocampal neurogenesis is essential for learning and memory. Hippocampal neural precursor cells (NPCs) can be induced to proliferate and differentiate into either glial cells or dentate granule cells. Notably, hippocampal neurogenesis decreases dramatically with age, partly due to a reduction in the NPC pool and a decrease in their proliferative activity. Alpha-melanocyte-stimulating hormone (α-MSH) improves learning, memory, neuronal survival and plasticity. Here, we used postnatally-isolated hippocampal NPCs from Wistar rat pups (male and female combined) to determine the role of the melanocortin analog [Nle, D-Phe]-α-MSH (NDP-MSH) in proliferation and fate acquisition of NPCs. Incubation of growth-factor deprived NPCs with 10 nM NDP-MSH for 6 days increased the proportion of Ki-67- and 5-bromo-2'-deoxyuridine (BrdU)-positive cells, compared to the control group, and these effects were blocked by the MC4R antagonist JKC-363. NDP-MSH also increased the proportion of glial fibrillar acidic protein (GFAP)/Ki-67, GFAP/ sex-determining region Y-box2 (SOX2) and neuroepithelial stem cell protein (NESTIN)/Ki-67-double positive cells (type-1 and type-2 precursors). Finally, NDP-MSH induced peroxisome proliferator-activated receptor (PPAR)-γ protein expression, and co-incubation with the PPAR-γ inhibitor GW9662 prevented the effect of NDP-MSH on NPC proliferation and differentiation. Our results indicate that in vitro activation of MC4R in growth-factor-deprived postnatal hippocampal NPCs induces proliferation and promotes the relative expansion of the type-1 and type-2 NPC pool through a PPAR-γ-dependent mechanism. These results shed new light on the mechanisms underlying the beneficial effects of melanocortins in hippocampal plasticity and provide evidence linking the MC4R and PPAR-γ pathways in modulation of hippocampal NPC proliferation and differentiation.
PubMed: 38960135
DOI: 10.1016/j.neuropharm.2024.110058 -
The Journal of Biological Chemistry Jul 2024Previous studies suggest that uric acid or reactive oxygen species, products of xanthine oxidoreductase (XOR), may associate with neurodegenerative diseases. However,...
Previous studies suggest that uric acid or reactive oxygen species, products of xanthine oxidoreductase (XOR), may associate with neurodegenerative diseases. However, neither relationship has ever been firmly established. Here, we analyzed human brain samples, obtained under protocols approved by research ethics committees, and found no expression of XOR and only low levels of uric acid in various regions of the brain. In the absence of XOR, hypoxanthine will be preserved and available for incorporation into the purine salvage pathway. To clarify the importance of salvage in the brain, we tested using human induced pluripotent stem cell-derived neuronal cells. Stable isotope analyses showed that the purine salvage pathway was more effective for ATP synthesis than purine de novo synthesis. Blood uric acid levels were related to the intracellular adenylate pool (ATP + ADP + AMP), and reduced levels of this pool result in lower uric acid levels. XOR inhibitors are related to extracellular hypoxanthine levels available for uptake into the purine salvage pathway by inhibiting the oxidation of hypoxanthine to xanthine and uric acid in various organs where XOR is present and can prevent further decreases in the intracellular adenylate pool under stress. Furthermore, adding precursors of the pentose phosphate pathway enhanced hypoxanthine uptake, indicating that purine salvage is activated by PRPP replenishment. These findings resolve previous contradictions regarding XOR products and provide new insights into clinical studies. It is suggested that therapeutic strategies maximizing maintenance of intracellular adenylate levels may effectively treat pathological conditions associated with ischemia and energy depletion.
PubMed: 38960035
DOI: 10.1016/j.jbc.2024.107524 -
Food Chemistry Jun 2024The lipids and volatile compounds in pork from different parts, including the loin, belly, shoulder and hind leg were analyzed by triple quadrupole tandem time-of-flight...
The lipids and volatile compounds in pork from different parts, including the loin, belly, shoulder and hind leg were analyzed by triple quadrupole tandem time-of-flight mass spectrometer (Q-TOF/MS) and gas chromatography-olfactometry-mass spectrometry (GC-O-MS), respectively. Partial least squares regression (PLSR) and Pearson correlation analysis were utilized to establish the relationship between the lipids and volatile compounds. A total of 8 main flavour substances, 38 main phospholipids, and 32 main fatty acids were identified. The results showed that the key flavour compounds were mainly derived from unsaturated fatty acids and phospholipids containing unsaturated fatty acids, including oleic acid (C18:2n6c), α-Linolenic acid (C18:3n3), arachidonic acid (C20:4n6), PE O (18:1/20:4), PE O (18:2/20:4), and PE O (18:2/18:2), etc. Understanding the relationship between flavour compounds and lipids of pork will be helpful to control the quality of pork.
PubMed: 38959797
DOI: 10.1016/j.foodchem.2024.139422 -
Talanta Jun 2024Methamphetamine (MA) is one of the most virulent illicit drugs that can be synthesized from household materials leading to its prevalent trafficking and local...
Methamphetamine (MA) is one of the most virulent illicit drugs that can be synthesized from household materials leading to its prevalent trafficking and local manufacturing in clandestine drug laboratories (clan labs). The significant problems of tracing MA in clan labs and monitoring drug abusers lie in the lag time between sample collection and analysis and the number of tests done. Capillary electrophoresis (CE) is a rapid separation technique amenable to miniaturization and field testing. Herein, we developed a simple transient isotachophoretic (tITP)-CE method to detect MA and its precursor pseudoephedrine (PSE) in clan labs and non-invasive biological fluids. The method was implemented on the ETD-100, a commercial fully automated portable CE instrument with an integrated swab-based extraction system. Within 2 min of insertion of the swab, MA and PSE were automatically extracted with a leading electrolyte (LE) and then separated on covalently modified capillaries. The ETD-100 showed a limit of detection (LOD) and quantification (LOQ) of MA 0.02 and 0.05 μg/swab and 0.02 and 0.06 μg/swab of PSE, with an enhancement factor of 118 and 328, respectively, when compared to a normal non-tITP injection. The intra and inter-day relative standard deviation in terms of migration time were in the range of 0.75-1.93 % for both MA and PSE and were 2.0-2.4 % for both MA and PSE peak height. The method was demonstrated with the detection of spiked MA and PSE on different household materials as well as in non-invasive biological fluids with a recovery above 60 %.
PubMed: 38959669
DOI: 10.1016/j.talanta.2024.126357 -
International Journal of Gynecological... Jul 2024Knowledge about the morphologic and molecular characteristics of cervical squamous cell carcinomas (CSCCs) associated with uterine prolapse is very limited. Detailed...
Knowledge about the morphologic and molecular characteristics of cervical squamous cell carcinomas (CSCCs) associated with uterine prolapse is very limited. Detailed histopathological and immunohistochemical (p16, p53, and cytokeratin 17), as well as molecular evaluation for human papillomavirus (HPV)-DNA and p53-mutational analyses in 4 consecutive CSCCs associated with uterine prolapse with definition of a hitherto not well-described HPV-independent/p53abnormal precursor lesion (HPV-independent cervical intraepithelial neoplasia [CIN; differentiated CIN]) and molecular tumorigenetic pathway. Cases diagnosed within 7 years with a mean age of 75 (range: 69-83) years and a mean tumor size of 7.3 cm (range: 5.2-9.4 cm). All patients presented with locally advanced disease, and 1 woman died of the disease within 4, and another within 14 months of follow-up. All CSCCs and their adjacent precursor lesions were negative for p16, with aberrant p53-expression and diffuse and strong staining for cytokeratin 17. Both the CSCCs and their precursors were negative for HPV-DNA but harbored a TP53 mutation. The precursor lesions were characterized by epithelial thickening with superficial keratinization, and the presence of basal and parabasal keratinocytes with mitotic figures beyond the basal layer, thus showing features similar to those seen in differentiated types of vulvar intraepithelial lesions (vulvar intraepithelial neoplasia [VIN] syn. HPV-independent/p53abn VIN), suggesting the terminology of differentiated CIN or HPV-independent/p53abn CIN. An HPV-independent pathogenetic pathway with a p53-alteration was identified for these cases. CSCC associated with uterine prolapse represents HPV-independent tumors harboring a TP53 mutation. For the first time, a precursor lesion of HPV-independent CSCC of the uterine cervix is described with a differentiated VIN-like morphology, and a separate tumorigenic pathway defined.
PubMed: 38959413
DOI: 10.1097/PGP.0000000000001040 -
Journal of the American Chemical Society Jul 2024Dirhodium tetrakis(2,2'-binaphthylphosphate) catalysts were successfully developed for asymmetric C-H functionalization with trichloroethyl aryldiazoacetates as the...
Dirhodium tetrakis(2,2'-binaphthylphosphate) catalysts were successfully developed for asymmetric C-H functionalization with trichloroethyl aryldiazoacetates as the carbene precursors. The 2,2'-binaphthylphosphate (BNP) ligands were modified by introduction of aryl and/or chloro functionality at the 4,4',6,6' positions. As the BNP ligands are C-symmetric, the resulting dirhodium tetrakis(2,2'-binaphthylphosphate) complexes were expected to be D-symmetric, but X-ray crystallographic and computational studies revealed this is not always the case because of internal T-shaped CH-π and aryl-aryl interactions between the ligands. The optimum catalyst is Rh(-megaBNP), with 3,5-di(-butyl)phenyl substituents at the 4,4' positions and chloro substituents at the 6,6' positions. This catalyst adopts a D-symmetric arrangement and is ideally suited for site-selective C-H functionalization at unactivated tertiary sites with high levels of enantioselectivity, outperforming the best dirhodium tetracarboxylate catalyst developed for this reaction. The standard reactions were conducted with a catalyst loading of 1 mol % but lower catalyst loadings can be used if desired, as illustrated in the C-H functionalization of cyclohexane in 91% ee with 0.0025 mol % catalyst loading (29,400 turnover numbers). These studies further illustrate the effectiveness of donor/acceptor carbenes in site-selective intermolecular C-H functionalization and expand the toolbox of catalysts available for catalyst-controlled C-H functionalization.
PubMed: 38959398
DOI: 10.1021/jacs.4c06023 -
Cancer Research Jul 2024The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial-mesenchymal transition (EMT), which promotes...
The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial-mesenchymal transition (EMT), which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the de novo serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin+ breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of PHGDH, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin+ breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.
PubMed: 38959339
DOI: 10.1158/0008-5472.CAN-23-3082 -
Clinical Infectious Diseases : An... Jul 2024Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish...
BACKGROUND
Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed.
METHODS
Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey.
RESULTS
Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%-5.01%), with highest rates observed in individuals screened for anal and colorectal cancers.
CONCLUSIONS
The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.
PubMed: 38959300
DOI: 10.1093/cid/ciae359 -
The Journal of General Virology Jul 2024is a family for negative-sense RNA viruses with genomes of about 9.7-15.8 kb. These viruses are maintained in and/or transmitted by insects. Phasmavirids produce...
is a family for negative-sense RNA viruses with genomes of about 9.7-15.8 kb. These viruses are maintained in and/or transmitted by insects. Phasmavirids produce enveloped virions containing three single-stranded RNA segments that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family which is available at ictv.global/report/phasmaviridae.
Topics: Genome, Viral; Animals; RNA, Viral; Negative-Sense RNA Viruses; Virion; Viral Proteins; Insecta; Phylogeny; Virus Replication
PubMed: 38959049
DOI: 10.1099/jgv.0.002002 -
Environmental Science and Pollution... Jul 2024Nanoparticles, owing to their unique physicochemical properties, have garnered significant attention in various scientific disciplines, including materials science,...
Green-synthesized CuO and ZnO nanoparticles derived from Calotropis gigantea (Apple of Sodom): enhancing plant growth, efficient dye removal, and potent antibacterial applications.
Nanoparticles, owing to their unique physicochemical properties, have garnered significant attention in various scientific disciplines, including materials science, chemistry, biology, and environmental engineering. In recent years, the synthesis of metal oxide nanoparticles, such as NiO, FeO, ZnO, SnO, and CuO via green routes, has gained attraction due to their diverse applications in fields ranging from catalysis and electronics to medicine and environmental remediation. This study focuses on the green synthesis of copper oxide (CuO) and zinc oxide (ZnO) nanoparticles using Calotropis gigantea (Apple of Sodom) leaf extract as a reducing agent and stabilizer, with zinc nitrate (ZnNO.6HO) and copper nitrate (CuNO.3HO) as precursors. The hexagonal phase of ZnO and monoclinic plan structure of CuO with high crystallinity was confirmed by XRD and elemental composition by EDX analysis. With the help of an SEM image, particle size measured for CuO and ZnO using ImageJ software was found to be 56.08 nm and 46.49 nm, respectively. This study investigates the efficacy of nanoparticles in wastewater treatment, particularly focusing on methylene blue dye decolorization using the statistical processing of response surface methodology (RSM) using the Box-Behnken method. Additionally, it explores the impact of synthesized nanoparticles on seed growth enhancement, using Vigna radiata (green gram) seeds immersed in various doses of nanoparticles (0, 0.5, 1, 1.5, 2 mg/30 mL). Furthermore, the antibacterial activity of the nanoparticles against both gram-positive and gram-negative bacteria is evaluated. The results confirm the effectiveness of the materials for methylene blue dye removal, achieving 80.53% with CuO and 78.25% with ZnO. Significant seed growth was observed with a low nanoparticle dosage of 1.5 mg/30 mL, resulting in the highest seedling vigour index and germination percentage. This reduces the need for fertilizers and lessens environmental impact.
PubMed: 38958855
DOI: 10.1007/s11356-024-34053-8