BioMed Research International最新文献

Aim: The aim of this study is to examine the prevalence of molar incisor hypomineralization (MIH), as well as the relationship between stimulated salivary flow rate, salivary pH, viscosity, and salivary buffer capacity with the presence of MIH in 6- to 12-year-old Mexican children.

Material and methods: Cross-sectional study conducted on 296 6- to 12-year-old schoolchildren selected from a public primary school. Saliva samples were collected and analyzed for resting salivary flow rate, salivary pH, stimulated salivary flow rate, viscosity, and salivary buffer capacity, using the Saliva-Check BUFFER kit. MIH was evaluated using the European Academy of Paediatric Dentistry criteria (EAPD).

Results: The prevalence of MIH was found to be 27.7%, whereas 42.9% of participants presented poor oral hygiene. Only four salivary parameters were observed to be associated with the presence of MIH. The probability of the occurrence of MIH was significantly higher in children presenting a high level of salivary viscosity (OR = 2.39; p = 0.007), a moderately acidic salivary pH (OR = 2.98; p = 0.001), a low/very low stimulated salivary flow rate (OR = 2.49; p = 0.006), and a low/very low salivary buffer capacity (OR = 4.24; p < 0.001).

Conclusions: A relationship was found between stimulated salivary flow rate, salivary pH, viscosity, and salivary buffer capacity and the presence of MIH in Mexican children. Specific strategies and interventions using remineralizing agents are required to improve both salivary health and the remineralization of teeth damaged by MIH in the child population.

Protein tyrosine phosphatase 1B (PTP1B) is a crucial drug target for treating diabetes mellitus Type 2 (DMT2) because of its link to insulin resistance. Currently there are no approved clinical drugs targeting PTP1B. Therefore, the present study was aimed at investigating the mode of action of an alkaloid, 1, 2-dimethoxy-12-methyl-7-(3-methylbut-2-en-1-yl)-12, 13-dihydro [1,3] benzodioxolo [5,6-c] phenanthridin-13-ol (1, 2 DMMDBP), previously isolated from a popular Zimbabwean antidiabetic herbal medicine. Molecular docking studies using PDB, 2QBP (catalytic site) and IT48 (allosteric site), in vitro PTP1B enzyme inhibition, and in vivo assays using streptozotocin induced diabetic rats were applied to investigate antidiabetic effect. Drug-like and toxicity properties were evaluated using SwissADME and Protox 3.0 webservers, respectively. Molecular docking results showed that the test compound (1, 2 DMMDBP) has a greater binding affinity (11.1 kcal/mol, rmsd, 0.000 Å) for the allosteric site than the catalytic site (9.6 kcal/mol, rmsd, 0.000 Å). In vitro inhibition assay showed that 1, 2 DMMDBP was more potent (IC50 = 1.10 μM) than that of ursolic acid (IC50 = 7.13 μM). Additionally, in in vivo studies, 1, 2 DMMDBP maintained normal hypoglycemia and mass better than the reference drug metformin. In absorption, distribution, metabolism, and excretion predictive studies, 1, 2 DMMDBP showed good drug-like properties. It did not violate any of Lipinski's classic rules. It showed good physicochemical properties such as absorption, (log of skin permeability (log Kp) value was -4.95), bioavailability with a score of 0.55 and biotransformation by cytochrome-P enzymes CYP1A2 and CYP3A4. Protox 3.0 webserver predicted LD₅₀ value of 1000 mg/kg, showing that it may be toxic if swallowed. Based on the evidence presented, 1, 2 DMMDBP is a highly promising compound in the development of potent and selective allosteric modulator drugs of PTP1B for the treatment of DMT2 upon further studies.

Anisomeles indica is widely used in traditional medicine and functional foods; however, its toxicological safety has not been systematically evaluated. This study evaluated the genotoxicity and subacute oral toxicity of a standardized A. indica-containing powder (AIHP) using OECD-compliant test guidelines. Genotoxicity was assessed via the bacterial reverse mutation test (OECD 471), in vitro chromosomal aberration test (OECD 473), and in vivo micronucleus assay in mice (OECD 474). A repeated-dose 28-day oral toxicity study (OECD 407) was performed in Sprague-Dawley rats at doses of 2000, 4000, and 8000 mg/kg/day. AIHP did not induce mutagenicity, chromosomal aberrations, or micronucleus formation in any assay. No treatment-related mortality, clinical signs, or adverse changes in body weight, hematology, serum biochemistry, organ weights, urinalysis, or histopathology were observed. The no-observed-adverse-effect level (NOAEL) was established at 8000 mg/kg/day. These results support the toxicological safety of AIHP and its suitability for use as a health food ingredient.

The cross-reactivity of substrates, modulators with other enzymes significantly reduces/prevents our ability to design such highly specific, that is, "one warhead-one target", modulators. On the other hand, the potential "impasse" fuels repurposing of already developed drugs. Additionally, expanding our understanding that there will be "off-target" effects for enzymes of different evolutionary kingdoms propels the development of covalent reversible drugs. In this review/perspective, we examine these challenges and opportunities based on covalent drugs used/developed for targeting bacterial and mammalian enzymes, and our evolving understanding of the blurred difference between these enzymes in these "vastly" separated organisms by biological evolution.

Background: Hepatitis B virus (HBV) infection remains a critical global health issue, affecting over 254 million individuals and causing approximately 1.2 million new infections annually. This systematic review and meta-analysis is aimed at estimating the pooled prevalence of HBV infection and identifying associated risk factors among pregnant women in West African countries.

Methods: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched Ovid Medline, Ovid Global Health, Ovid Embase, Web of Science, African Journals Online (AJOL), and African Index Medicus for studies on HBV infection in pregnant women in West African countries. We assessed the methodological quality of the included studies using the Hoy et al. tool. The random-effects model was used to calculate the pooled prevalence of HBV infection, whereas the I² statistic quantified heterogeneity. Egger's test and funnel plots evaluated publication bias.

Results: This analysis included 138 studies from 11 West African countries. The pooled prevalence of HBV infection, based on HBsAg seropositivity, was 8.0% (95% CI: 7.3-8.6), with significant heterogeneity between studies (I² = 96.8%, p < 0.001). The prevalence of HBeAg was 15% (95% CI: 10.5-19.9, I² = 79.3%, p < 0.01). HBV prevalence did not significantly differ between pregnant women with a history of blood transfusion or dental care compared with those without these exposures. Body tattoos were associated with HBV infection, with an odds ratio of 2.28 (95% CI: 1.08-4.79).

Conclusion: This systematic review reveals a substantial prevalence of HBV infection among pregnant women in West Africa, underscoring the urgent need to enhance prevention efforts. Improved access to diagnostic testing and vaccination remains essential to achieving HBV elimination in this population.

Aim: This study was aimed at comparing the effects of a driving-related combined exercise and cognitive training system intervention on frontal lobe function in older adults with an active control group that performed aerobic exercises.

Methods: In this randomized controlled trial, 90 community-dwelling older adults were randomly allocated (1:1) to the intervention (n = 45) or control groups (n = 45). The intervention group participated in a combined exercise-cognitive multitask training program for six consecutive weeks, whereas the active control group performed matched-intensity aerobic exercises during the same period. Cognitive function was assessed using the Trail Making Test Parts A and B (TMT-A and B) and the Frontal Assessment Battery (FAB). Changes in the hemodynamics of the frontopolar cortex (FPC) during the task were measured using portable functional near-infrared spectroscopy (fNIRS). Assessments were conducted at baseline, postintervention, and follow-up time points.

Results: The final analysis included 44 and 40 participants in the intervention and control groups, respectively. TMT-A and B results and FAB scores showed no significant differences between the groups at any time point. Similarly, fNIRS analysis showed no significant differences in hemodynamic reactivity in the FPC between the intervention and active control groups.

Conclusions: This study demonstrated that the multitask training system did not confer additional benefits beyond aerobic exercise under a low-intensity, short-duration protocol in older adults, with no significant improvements in cognitive performance or frontopolar hemodynamic reactivity. Future studies should incorporate extended intervention periods and evaluate outcomes in diverse demographic populations to establish the additional advantages of driving behavior-related multitask training compared with aerobic exercises.

The investigation into the anticancer properties of plant extracts, which are known to be effective therapeutic agents with minimal side effects, is gaining significant traction. The current study examined the bioactive compounds extracted from Sapium ellipticum and Salvia miltiorrhiza Bunge. Salvianolic acid (Sal B), ellagic acid (EA), [20-³H]-12-deoxyphorbol-13-isobutyrate ([³H] DPB), and [20-³H] phorbol-12, 13-dibutyrate ([³H] PDBu) have all been analyzed in vitro and in silico. Based on the molecular docking simulations, Sal B targeted DNA lyase, topoisomerase II alpha, and mTOR, with docking scores of -9.5, -6.9, and -7.9 kcal/mol, respectively. The docking scores of these compounds were comparable with those of EA, which had a docking score of -8.7, -6.5, and -7.6 kcal/mol when targeting DNA lyase, topoisomerase II alpha, and mTOR, respectively. Remarkably, Sal B (-9.0 kcal/mol), EA (-7.6 kcal/mol), [3H] PDBu (-8.7 kcal/mol), and [3H] DPB (-7.1 kcal/mol) showed weaker binding affinities to the mTOR kinase enzyme compared with rapamycin (-11.2 kcal/mol). With an IC₅₀ of 11.6 μM, Sal B demonstrated remarkable efficacy and was almost as effective as the common inhibitor rapamycin (IC₅₀ of 5.2 μM). With an IC₅₀ of 21.9 μM, EA demonstrated a mild but similar inhibition. The assay and docking results were validated by the root mean square deviation (RMSD) plots of Sal B and EA, which demonstrated that they are both kinetically stable. The results of this study present a promising pathway for the advancement of therapeutic agents targeting breast cancer (BC) and prostate cancer (PCa). Eventually, these bioactive compounds will require precise clinical studies and in vivo testing to confirm their possible preventive and curative action.

This study assessed the clinical response and adverse effects of lithium in patients with bipolar disorder (BD) at Amanuel Mental Specialized Hospital (AMSH) in Addis Ababa, Ethiopia. A retrospective cohort and cross-sectional design were employed as part of the Neuropsychiatric Genetics of African Populations (NeuroGAP)-Psychosis, Ethiopia project including 262 patients on lithium therapy for at least 6 months; adverse effects were evaluated in 157 of them. Clinical response was measured using the Alda scale, and adverse effects were assessed via a structured questionnaire. Among the participants, 27.5% were classified as good responders (GRs), whereas the remaining 72.5% were classified as insufficient responders (IRs), comprising both partial and nonresponders. Significant differences were observed in age group, length of lithium therapy, concomitant therapy, and number of concomitant medications, with 33% of the IRs on lithium for 1-2 years compared to only 10% of the GRs; most patients in both groups had been on lithium for 2-5 years. Additionally, 83.2% of the IRs used other medications alongside lithium, with 78% using just one additional medication. Logistic regression found that age (p = 0.008), concurrent use of other psychiatric medications (p < 0.001), and stable lithium plasma levels (p = 0.003) were significantly associated with lithium response. Regarding adverse effects, 58.6% of patients reported at least one adverse event, with tremors, excessive thirst, and frequent urination being the most common. Age, tobacco use, and treatment duration were associated with lithium adverse effects, with younger age and tobacco use linked to higher risk, whereas older age and longer treatment were associated with fewer adverse effects. In conclusion, the findings highlight the importance of monitoring use of psychiatric concomitant medications and plasma lithium levels to improve outcomes in BD patients on lithium.

Introduction: Cancer remains the leading cause of death worldwide, with breast cancer being the most prevalent disease diagnosed globally. Liver cancer is the fourth most common cause of death globally, while prostate cancer accounts for the second most frequent malignancy among males worldwide. The main treatment options for cancer include surgery, radiation therapy, and chemotherapy. The stem bark of Tieghemella heckelii has been exploited for its medicinal properties. On a broader scale, research on the anticancer properties of T. heckelii has not been explored. It is therefore important to investigate the anticancer potential of the leaves of T. heckelii. The goal of the study was to evaluate the in vitro anticancer activities of the leaves of T. heckelii on breast, prostate, and liver cancer cell lines.

Methods: The leaves of T. heckelii were collected from Asantemanso, Akim Oda, in the eastern region of Ghana. Authenticity of the leaves was performed at the Department of Plant and Environmental Biology, University of Ghana. Aqueous and ethanol extraction were performed on the leaves of T. heckelii after grinding into fine particles, followed by low-temperature drying. Breast cancer (MDA-MB-468), liver cancer (HepG2), and normal kidney (Vero E6) cell lines were cultured in DMEM media, while prostate cancer (PC3) cell lines were cultured in RPMI medium. Anticancer activity of the leaves of T. heckelii was conducted on breast (MDA-MB-468), liver (HepG2), and prostate (PC3) cancer cell lines. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method.

Results: Both ethanolic and aqueous extracts demonstrated similar cytotoxicity for the HepG2 cell line, with IC₅₀ values of about 200 μg/mL. selectivity index of > 2 was recorded by all cell lines. When compared to other cell lines, the aqueous extract for prostate cancer showed the lowest IC₅₀ value with a selectivity of 8. In addition, the extracts showed less cytotoxic activity against the normal (Vero) cell line.

Conclusion: Leaves of T. heckelii possess cytotoxic properties with notable selectivity against prostate (PC3) and liver (HepG2) cancer cell lines. However, findings should be evaluated in in vivo studies because biological processes can be more complex in living organisms. Further investigation should be conducted to ascertain the bioactive compounds responsible for the anticancer activity.