Monolithic Endocrown Vs. Hybrid Intraradicular Post/Core/Crown Restorations for Endodontically Treated Teeth; Cross-sectional Study

The gold standard for restoring Endodontically Treated Teeth (ETT) with successful clinical longevity requires having minimal invasive preparations and maximal tissue conservation. Many dentists still consider hybrid post/core/crown to be the first choice for restoring ETT. Endocrown is a viable alternative treatment modality to hybrid post/core/crown. This study aims to assess the proper judgment of dentists working in Riyadh, Saudi Arabia on the use of monolithic endocrown versus hybrid post/core/crown for restoring ETT. The IRB of Princess Nourah Bint Abdulrahman University (PNU) Institutional Review Board reviewed this study. The questionnaire was validated and electronically distributed. The participants were pre-informed that their responses are completely anonymous and used for professional purposes only. The questionnaire surveyed dentists working in Riyadh, Saudi Arabia, about their preference for different ETT restorative modalities at various clinical scenarios. Data were analyzed using One-way ANOVA and t-test. All P-values of < 0.05 were considered statistically significant. A total of 275 responses were collected; 61.45% were females and 38.55% males. 56% of them were general practitioners, while 16% were consultants. Prefabricated post/core was the most preferred technique among the participants (18.55%), followed by endocrown (12.36%), and lastly, cast post/core (8.73%). The amount of remaining tooth structure was the most influential in the treatment selection (30.18%), followed by the presence or absence of 1–2 mm ferrule (17.82%). Interocclusal space (12.36%) was the least influential factor. Endocrown recorded 63.27% as the most preferred line of treatment in case of insufficient inter-occlusal space. 40.36% preferred endocrown for patients with occlusal risk factors. The amount of the remaining tooth structure and the tooth position significantly affect the treatment options of the participants. Endocrown was the most preferred treatment modality for restoring ETT for patients with occlusal consideration.     

BCL-2 antisense and cisplatin combination treatment of MCF-7 breast cancer cells with or without functional p53

Summary Chemotherapy has been used for treatment of breast cancer but with limited success. We characterized the effects of bcl-2 antisense and cisplatin combination therapy in two human isogenic breast carcinoma cells p53(+)MCF-7 and p53(−)MCF-7/E6. The transferrin-facilitated lipofection strategy we have developed yielded same transfection efficiency in both cells. Bcl-2 antisense delivered with this strategy significantly induced more cell death, apoptosis, and cytochrome c release in MCF-7/E6 than in MCF-7, but did not affect Fas level in both cells and activated caspase-8 equally. Cisplatin exerted same effects on cell viability and apoptosis in both cells, but released smaller amounts of cytochrome c while activated more caspase-8 in MCF-7/E6. The combination treatment yielded greater effects on cell viability, apoptosis, cytochrome c release, and caspase-8 activation than individual treatments in both cells although p53(−) cells were more sensitive. The potentiated activation of caspase-8 in the combination treatment suggested that caspase-8-mediated (but cytochrome c-independent) apoptotic pathway is the major contributor of the enhanced cell killing. Thus, bcl-2 antisense delivered with transferrin-facilitated lipofection can achieve the efficacy of killing breast cancer cells and sensitizing them to chemotherapy. Bcl-2 antisense and cisplatin combination treatment is a potentially useful therapeutic strategy for breast cancer irrespective of p53 status. Hesham Basma and Hesham El-Refaey contributed equally     

l-DOPA Cytotoxicity to PC12 Cells in Culture Is via Its Autoxidation

Abstract: The mechanism of cytotoxicity of l -DOPA was studied in the rat pheochromocytoma PC12 cell line. The cytotoxicity of l -DOPA to PC12 cells was time and concentration dependent. Carbidopa, which inhibited the conversion of l -DOPA to dopamine, did not protect against l -DOPA cytotoxicity in PC12 cells. Furthermore, clorgyline, a selective inhibitor of monoamine oxidase type A, and pargyline, an inhibitor of both monoamine oxidase types A and B, both did not have an effect on l -DOPA toxicity. These findings suggest that cytotoxicity was not due to dopamine formed from l -DOPA. Catalase or superoxide dismutase each partially protected against l -DOPA toxicity in PC12 cells. In combination, the effects were synergistic and provided almost total protection against cytotoxicity. 6-Cyano-7-nitroquinoxaline-2,3-dione, an antagonist of non-NMDA receptors, did not protect against l -DOPA toxicity. These data suggest that toxicity of l -DOPA is most likely due to the action of free radicals formed as a result of its autoxidation. Furthermore, these findings suggest that patients on long-term l -DOPA therapy are potentially at risk from the toxic intermediates formed as a result of its autoxidation.     

Vascular architecture and patchy nutrient availability generate within-plant heterogeneity in plant traits important to herbivores

Within-plant heterogeneity in growth, morphology, and chemistry is ubiquitous, and is commonly attributed to differences in tissue age, light availability, or previous damage by herbivores. Although these factors are important, we argue that plant vascular architecture is an underappreciated determinant of heterogeneity. Vascular architecture can restrict the transport of resources (nutrients, photosynthate, hormones, etc.) to within specific sectors of the plant: this is referred to as sectoriality. Although studies have documented sectoriality in the transport of isotopes and dyes from roots to shoots, the ecological consequences of this sectoriality remain poorly understood. We tested the hypothesis that spatial variation in belowground nutrient availability combined with sectorial transport results in localized "fertilization" of aboveground plant parts and generates heterogeneity in traits important to herbivores. Our split-root experiments with tomato (Lycopersicon esculentum Mill) clearly demonstrate that fertilization to isolated lateral roots generates heterogeneity in leaf morphology, phenolic chemistry, and side-shoot growth. Specifically, leaflets with direct connections to these lateral roots were larger and had lower levels of rutin and chlorogenic acid than did leaflets in other sectors lacking direct vascular connections. Moreover, side-shoot production was greater in the connected sectors. We discuss the implications of this heterogeneity for plant-herbivore interactions.     

The Potential Efficacy of Glycyrrhizic Acid and Its Nanostructure Against Brown Rot of Peach fruits

Production of peaches (Prunus persica (L.) Batsch) for both local market and export is increasing each year in Egypt. Brown rot disease, caused by Monilinia laxa and Monilinia fructigena, is considered one of the most important postharvest rots affecting peaches in Egypt and economic losses are increasing. Antifungal activity of glycyrrhizic acid nanoparticles (GA-NPs) and glycyrrhizic acid (GA) at 0.2 and 0.4 mmol/L was investigated as a control for both these brown rot pathogens on peach fruits in both in vitro and in vivo studies. In the in vitro studies, GA-NPs were the most effective as shown by the ability to decrease linear growth of both brown rot pathogens in potato dextrose agar (PDA) amended with 0.4 mmol/L GA-NPs. Micrographs of M. fructigena exposed to 0.4 mmol/LGA showed mycelial deformations, nodule formation, detachment of the cell wall, shrinkage and inhomogeneous cytoplasmic materials with large vacuoles. Mycelium of M. laxa exposed to 0.4 mmol/ LGA-NPs resulted in thinner and distorted hyphae, nodule formation, cell wall thinning, and swellings. The GANPs and GA treatments improved fruit quality by maintaining firmness and total soluble solids (TSS). GA-NPs were more effective in decreasing decay incidence than their bulk material. The 0.4 mmol/L GA-NPs completely inhibited the disease on naturally infected peach fruits for both seasons of 2018 and 2019. Furthermore, 0.4 mmol/L GA-NPs reduced the disease incidence in inoculated fruits by 95 (M. laxa) and 88% (M. fructigena) in 2018 season and 96 (M. laxa) and 85% (M. fructigena) in 2019 season. In conclusion, GA-NPs could enhance the resistance of peaches against brown rot caused by M. laxa and M. fructigena.     

Integrated multi-omics analysis reveals unique signatures of paclitaxel-loaded poly(lactide-co-glycolide) nanoparticles treatment of head and neck cancer cells

The use of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) as carriers for chemotherapeutic drugs is regarded as an actively targeted nano-therapy for the specific delivery of anti-cancer drugs to target cells. However, the exact mechanism by which PLGA NPs boost anticancer cytotoxicity at the molecular level remains largely unclear. This study employed different molecular approaches to define the response of carcinoma FaDu cells to different types of treatment, specifically: paclitaxel (PTX) alone, drug free PLGA NPs, and PTX-loaded PTX-PLGA NPs. Functional cell assays revealed that PTX-PLGA NPs treated cells had a higher level of apoptosis than PTX alone, whereas the complementary, UHPLC-MS/MS (TIMS-TOF) based multi-omics analyses revealed that PTX-PLGA NPs treatment resulted in increased abundance of proteins associated with tubulin, as well as metabolites such as 5-thymidylic acid, PC(18:1(9Z)/18:1(9Z0), vitamin D, and sphinganine among others. The multi-omics analyses revealed new insights about the molecular mechanisms underlying the action of novel anticancer NP therapies. In particular, PTX-loaded NPs appeared to exacerbate specific changes induced by both PLGA-NPs and PTX as a free drug. Hence, the PTX-PLGA NPs’ molecular mode of action, seen in greater detail, depends on this synergy that ultimately accelerates the apoptotic process, resulting in cancer cell death.     

Dry season distribution of land crabs, Gecarcinus quadratus (Crustacea: Gecarcinidae), in Corcovado National Park, Costa Rica

The land crab Gecarcinus quadratus is an engineering species that controls nutrient cycling in tropical forests. Factors regulating their coastal distribution are not fully understood. We quantified land crab distribution during the dry season at Sirena Field Station in Corcovado National Park, Costa Rica, and found that land crab burrow density decreases with increasing distance from the ocean. Leaf litter depth and tree seedling density are negatively correlated with land crab burrow density. Burrows are strongly associated with sand substrate and burrow density is comparatively low in clay substrate. Results suggest that G. quadratus is limited to a narrow coastal zone with sand substrate, and this distribution could have profound effects on plant community structure.     

Une nouvelle observation d’une métastase testiculaire d’un adénocarcinome prostatique: Aspects diagnostiques et éthiopathogéniques

Testicular metastases from prostatic adenocarcinoma are rare. They are often asymptomatic and diagnosed incidentally or at autopsy after orchidectomy in more advanced stages of the disease. The authors report a new case and review the diagnosis and aetiopathogenesis of these metastases. A 67-year-old patient with prostatic adenocarcinoma presented with painless right testicular mass for two months with no inflammatory signs. Germ cell tumour serum markers were negative. Scrotal ultrasound showed a large testicular tumour measuring 7×4×3cm. Histological examination revealed a solid non-differentiated tumour, not suggestive of primary testicular tumour. The immunohistochemical panel confirmed the prostate as the primary site due to the positivity of cytokeratins, PSA and PSAP and the negativity of classical markers of germ cell tumours. Testicular metastases from prostatic adenocarcinoma are rare, but their incidence is currently on the increase. They are often asymptomatic and discovered after pulpectomy. This diagnosis must be considered in the case of a testicular mass in patients over the age of 50 with a history of prostatic adenocarcinoma. The diagnosis was established after orchidectomy by histological examination and immunohistochemical tests.     

TRP channel–associated factors are a novel protein family that regulates TRPM8 trafficking and activity

TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity.