Small Molecule Induces Time-Dependent Inhibition of Stat3 Dimerization and DNA-Binding Activity and Regresses Human Breast Tumor Xenografts.

Aberrantly-active signal transducer and activator of transcription (Stat)3 has a causal role in many human cancers and represents a validated anticancer drug target, though it has posed significant challenge to drug development. A new small molecule, JKB887, was identified through library screening and is predicted to interact with Lys591, Arg609 and Pro63 in the phospho-tyrosine (pTyr)-binding pocket of the Stat3 SH2 domain. JKB887 inhibited Stat3 DNA-binding activity in vitro in a time-dependent manner, with IC of 2.

Bacterial structural genomics target enabled by a recently discovered potent fungal acetyl-CoA synthetase inhibitor.

The compound ethyl-adenosyl monophosphate ester (ethyl-AMP) has been shown to effectively inhibit acetyl-CoA synthetase (ACS) enzymes and to facilitate the crystallization of fungal ACS enzymes in various contexts. In this study, the addition of ethyl-AMP to a bacterial ACS from Legionella pneumophila resulted in the determination of a co-crystal structure of this previously elusive structural genomics target. The dual functionality of ethyl-AMP in both inhibiting ACS enzymes and promoting crystallization establishes its significance as a valuable resource for advancing structural investigations of this class of proteins.

Quantum evaluation and therapeutic activity of (E)-N-(4-methoxyphenyl)-2-(4-(3-oxo-3-phenylprop-1-en-1-yl) phenoxy)acetamide and its modified derivatives against EGFR and VEGFR-2 in the treatment of triple-negative cancer via in silico approach.

The most dangerous subtype of breast cancer, triple-negative breast cancer (TNBC), accounts for 25% of all breast cancer-related deaths and 15% of all breast cancer cases. TNBC is distinguished by the lack of immunohistochemical expression of HER2, progesterone receptors, or oestrogen receptors. Although it has been reported that upregulation of EGFR and VEGFR-2 is associated with TNBC progression, no proven effective targeted therapy exists at this time.

Novel Keto-Alkyl-Pyridinium Antifungal Molecules Active in Models of Candida albicans Vascular Catheter Infection and Candida auris Skin Colonization.

New antifungal therapies are needed for both systemic, invasive infections in addition to superficial infections of mucosal and skin surfaces as well as biofilms associated with medical devices. The resistance of biofilm and biofilm-like growth phases of fungi contributes to the poor efficacy of systemic therapies to nonsystemic infections. Here, we describe the identification and characterization of a novel keto-alkyl-pyridinium scaffold with broad spectrum activity (2 to 16 μg/mL) against medically important yeasts and molds, including clinical isolates resistant to azoles and/or echinocandins.

Novel keto-alkyl-pyridinium antifungal molecules active in models of in vivo vascular catheter infection and ex vivo skin colonization.

New antifungal therapies are needed for both systemic, invasive infections as well as superficial infections of mucosal and skin surfaces as well as biofilms associated with medical devices. The resistance of biofilm and biofilm-like growth phases of fungi contributes to the poor efficacy of systemic therapies to non-systemic infections. Here, we describe the identification and characterization of a novel keto-alkyl-pyridinium scaffold with broad spectrum activity (2-16 µg/mL) against medically important yeasts and moulds, including clinical isolates resistant to azoles and/or echinocandins.

Traditional Kenyan herbal medicine: exploring natural products' therapeutics against schistosomiasis.

Praziquantel (PZQ) remains the only drug of choice for the treatment of schistosomiasis, caused by parasitic flatworms. The widespread use of PZQ in schistosomiasis endemic areas for about four decades raises concerns about the emergence of resistance of Schistosoma spp. to PZQ under drug selection pressure.

Structural Characterization of the Reaction and Substrate Specificity Mechanisms of Pathogenic Fungal Acetyl-CoA Synthetases.

Acetyl CoA synthetases (ACSs) are cyl-CoA/RPS/uciferase (ANL) superfamily enzymes that couple acetate with CoA to generate acetyl CoA, a key component of central carbon metabolism in eukaryotes and prokaryotes. Normal mammalian cells are not dependent on ACSs, while tumor cells, fungi, and parasites rely on acetate as a precursor for acetyl CoA. Consequently, ACSs have emerged as a potential drug target.

Caregivers' perceptions of the oral-health-related quality of life of children with special needs in Johannesburg, South Africa.

Background: The prevalence of dental caries and its effect on the oral-health-related quality of life (OHRQoL) of children with special needs (CSNs) have not been established in South Africa.

Aim: The study aimed to assess how caregivers of CSNs who attended Down Syndrome Association outreach sites in Johannesburg, South Africa, perceived the contribution of OHRQoL to the quality of life of these children.

Setting: The study was conducted at Down Syndrome Association (DSA) outreach sites in Johannesburg.

Does nutrition have an effect on the timing of tooth formation?

Background: The effect of nutritional status on the timing of permanent tooth formation is not well understood, despite clear evidence that systemic stresses result in enamel defects during tooth formation.

Aim: This study investigated the effect of nutritional status (measured as BMI, height, weight, mid-upper arm circumference, and head circumference) on permanent tooth formation.

Method: This was a prospective cross-sectional study involving 642 (270 males, 372 females) healthy Black South African participants aged 5-20 years.

COMPARATIVE STUDY OF TREATMENT OUTCOME IN APICECTOMIES WITH OR WITHOUT ROOT-END FILLING.

Background: High success rate has been reported widely with conventional endodontic. When failure occurs, re-treatment alone or with surgical endodontics is the recommended treatment.

Objective: To compare the treatment outcome following apicectomy techniques, apicectomy with and without retrograde root - end filling.

Assessment of Self-Medication Practices and Its Associated Factors among Undergraduates of a Private University in Nigeria.

Background: Self-medication is the use of drugs to treat self-diagnosed disorders or symptoms or the intermittent or continued use of prescribed drug for chronic or recurrent disease or symptoms, and it is mostly common in developing countries. This study therefore assessed the practice of self-medication among undergraduate students of a private university in Nigeria.

Methods: The study employed a descriptive cross-sectional design.

The timing of permanent tooth development in a Black Southern African population using the Demirjian method.

Background: Many aspects of growth have been documented for Black Southern African children, yet their dental development has not been comprehensively investigated.

Aim: The present study was designed to provide information on age of attainment of dental development stages in Southern African children and to compare the findings with other populations.

Method: This was a community-based cross-sectional study of 642 children (270 males and 372 females).

Permanent tooth emergence: Timing and sequence in a sample of Black Southern African children.

Objectives: This study investigates mean age, sequence, and temporal trends of permanent tooth emergence in Black Southern African children and compares the findings with other population samples.

Materials And Methods: This community-based cross-sectional study involved 639 Black Southern African children between 5 and 20 years of age. Probit analysis was used to derive the mean age at emergence of the permanent teeth.

The WITS Atlas: A Black Southern African dental atlas for permanent tooth formation and emergence.

Unlabelled: Current dental maturity charts, such as the widely applied London atlas, do not take into consideration advanced tooth emergence and formation patterns observed in children of African ancestry. The result is inaccurate age estimation in Southern Africa, a region where there is great forensic and anthropological need for reliable age estimation.

Objectives: To develop a population-specific atlas of permanent tooth emergence and formation for age estimation of Black Southern Africans.

Accuracy of the Demirjian and Willems methods of age estimation in a Black Southern African population.

The accuracies of the original Demirjian, modified Demirjian and Willems dental age estimation methods were compared for a Black Southern African population to determine their usefulness for forensic and anthropological purposes. Data were collected using a community-based prospective study design. Panoramic radiographs of seven left mandibular teeth from 540 children aged 5-15.

The Demirjian versus the Willems method for dental age estimation in different populations: A meta-analysis of published studies.

Background: The accuracy of radiographic methods for dental age estimation is important for biological growth research and forensic applications. Accuracy of the two most commonly used systems (Demirjian and Willems) has been evaluated with conflicting results. This study investigates the accuracies of these methods for dental age estimation in different populations.

Efficacy of Three In-Office Dentin Hypersensitivity Treatments.

Purpose: This study assessed the comparative efficacy of three in-office treatment agents in patients presenting with dentin hypersensitivity (DH) at a university teaching hospital.

Materials And Methods: A randomised, controlled study was conducted to compare the efficacy of Gluma desensitiser, Pro-Relief and Copal F in relieving the pain of DH. In 68 subjects with 508 hypersensitive teeth, the agents and placebo (distilled water) were applied to 127 hypersensitive teeth each.

ISOLATION, CHARACTERIZATION AND IMMUNOCHEMICAL STUDIES ON FIBROUS PROTEINS FROM COWRY SHELL , LINNAEUS).

Background: Biomaterials are non-drug substances used to treat, enhance or replace functions of body tissues or organs. Natural sources of biomaterials have recently become the focus of several research activities. Cowry shell constitutes one of the most promising natural sources of biomaterials because of its chemical stability, biodegradability and biocompatibility in the body.

Masticatory efficiency of shortened dental arch subjects with removable partial denture: A comparative study.

Objective: The objective of this study was to compare the masticatory efficiency in subjects with shortened dental arch (SDA) before and after restoration with removable partial denture (RPD).

Materials And Methods: This was a prospective study carried out on 36 consecutive patients. The subjects were asked to chew 5 g of a measured portion of fresh raw carrot for 20 specified numbers of strokes.

Comparative evaluation of perceptions of dental students to three methods of teaching in Ile-Ife, Nigeria.

Background: The World Health Organization in 1994 recommended that dental education should be problem based, socially and culturally relevant, and community oriented.

Objectives: To explore the perceptions of Pre-phase II (pre-clinical II) dental students on three methods of teaching used during two academic sessions.

Methods: All part IV dental students in two consecutive sessions undergoing pre phase II course in the Faculty of Dentistry, Obafemi Awolowo University, Ile-Ife were recruited into the study.

Third molar impaction and agenesis: influence on anterior crowding.

Background Third molar influence on anterior crowding is controversial, but they are assumed to play a major role in compromising dental arch space. Aim To evaluate the relationship among impaction, agenesis and crowding in black South African males. Subjects and method Mandibles and maxillae of 535 black South African males in the Raymond A.

Prevalence, pattern and severity of molar incisor hypomineralisation in 8- to 10-year-old school children in Ile-Ife, Nigeria.

Aim: This study aimed to determine the prevalence, pattern and severity of MIH in school children resident in a suburban population in Nigeria.

Methods: This was a cross-sectional study involving pupils aged 8-10 years resident in suburban Nigeria. Details of each pupil's socio-demographic variables were collected.

Brief communication: Emergence chronology of permanent teeth in Nigerian children.

This study measured the mean age, duration, and sequence of the emergence of permanent dentition in Nigerian children and compared the findings with other population groups. The cross-sectional study involved 1,078 Nigerian children, aged 4-16 years old, from selected primary and secondary schools in the Ife Central local government area in Ile-Ife, Osun State. In general, compared to boys, girls had an earlier mean age of emergence of all the permanent teeth.