MicroRNAs and colorectal cancer: clinical potential and regulatory networks.

Colorectal cancer (CRC) is a serious global health concern, with a high incidence and mortality rate. Although there have been advancements in the early detection and treatment of CRC, therapy resistance is common. MicroRNAs (miRNAs), a type of small non-coding RNA that regulates gene expression, are key players in the initiation and progression of CRC. Recently, there has been growing attention to the complex interplay of miRNAs in cancer development. miRNAs are powerful RNA molecules that regulate gene expression and have been implicated in various physiological and pathological processes, including carcinogenesis. By identifying current challenges and limitations of treatment strategies and suggesting future research directions, this review aims to contribute to ongoing efforts to enhance CRC diagnosis and treatment. It also provides a comprehensive overview of the role miRNAs play in CRC carcinogenesis and explores the potential of miRNA-based therapies as a treatment option. Importantly, this review highlights the exciting potential of targeted modulation of miRNA function as a therapeutic approach for CRC.

Revolutionizing colorectal cancer treatment: unleashing the potential of miRNAs in targeting cancer stem cells.

Colorectal cancer (CRC) is a significant contributor to cancer mortality worldwide, and the presence of cancer stem cells (CSC) represents a major challenge for achieving effective treatment. miRNAs have emerged as critical regulators of gene expression, and recent studies have highlighted their role in regulating stemness and therapeutic resistance in CRC stem cells. This review highlights the mechanisms of CSC development, therapy resistance and the potential of miRNAs as therapeutic targets for CRC. It emphasizes the promise of miRNAs as a novel approach to CRC treatment and calls for further research to explore effective miRNA-based therapies and strategies for delivering miRNAs to CSCs in vivo.

Prevalence of vulvovaginal candidiasis among pregnant women in the Ho municipality, Ghana: species identification and antifungal susceptibility of Candida isolates.

BACKGROUND: Candida is the leading cause of vaginitis, and 75% of women have at least one episode of infection in their lives, with pregnancy being a predisposing factor. If left untreated, vulvovaginal candidiasis (VVC) can lead to chorioamnionitis with subsequent abortion, prematurity and congenital infection of the neonate. We aimed to determine the prevalence of VVC, identify the recent and most frequently occurring species of Candida in pregnant women, and determine the most effective antifungal drug of choice for treatment. METHOD: A prospective cross-sectional study in which 176 high vaginal swab samples of consented pregnant women visiting the antenatal clinic from February 2018 to April 2018 were subjected to direct gram smear and culture for Candida isolation. Candida isolates were identified using a germ tube test and HiCrome Candida differential agar. Candida isolates were then subjected to a disk diffusion method using fluconazole (25 µg), nystatin (100 units), and voriconazole (1 µg) on Mueller-Hinton agar supplemented with 2% (w/v) glucose and 0.5 µg/ml methylene blue dye to determine the susceptibility pattern as per the guidelines of the Clinical Laboratory Standard Institute (CLSI). Chi-square analysis was used to ascertain the significant association of participants' sociodemographics and clinical presentations to VVC. A univariate logistic regression model was used to identify potential risk factors of VVC. RESULTS: The prevalence of VVC among our study participants was 30.7%. Non-albicans Candida (NAC) and Candida albicans had a prevalence of 74.1 and 25.9%, respectively. Candida glabrata was the most common species, followed by Candida albicans, Candida krusei, and Candida parapsilosis. 50.0, 18.5 and 3.7% of Candida species were susceptible to voriconazole, fluconazole and nystatin, respectively, whereas 37.0, 48.1 and 9.3% of Candida species were resistant to voriconazole, fluconazole and nystatin, respectively. The majority of isolates were susceptible dose dependent to all three antifungal agents, with voriconazole being the most efficacious antifungal agent. There was no significant association between participants' socio-demographic information and clinical presentations to VVC. CONCLUSION: The prevalence of VVC was high in the study area. C. glabrata was found to be the most common cause of VVC among the pregnant women attending antenatal clinics, in the Ho Municipality region of Ghana. The majority of the Candida isolates were susceptible and resistant to voriconazole and fluconazole, respectively.

Pivotal Role of Cranial Irradiation-Induced Peripheral, Intrinsic, and Brain-Engrafting Macrophages in Malignant Glioma.

Malignant (high-grade) gliomas are aggressive intrinsic brain tumors that diffusely infiltrate the brain parenchyma. They comprise of World Health Organization (WHO) grade III and IV gliomas. Ionizing radiation or irradiation (IR) is frequently utilized in the treatment of both primary as well as metastatic brain tumors. On the contrary, macrophages (MΦ) are the most copious infiltrating immune cells of all the different cell types colonizing glioma. MΦ at tumor milieu are referred to as tumor-associated macrophages (TAMΦ). In malignant gliomas milieu, TAMΦ are also polarized into two distinct phenotypes such as M1 TAMΦ or M2 TAMΦ, which are capable of inhibiting or promoting tumor growth, respectively. Cranial-IR such as x- and γ-IR are sufficient to induce the migration of peripherally derived MΦ into the brain parenchyma. The IR facilitate a more immunosuppressive milieu via the stimulation of efferocytosis in TAMΦ, and an upsurge of tumor cell engulfment by TAMΦ exhibited detrimental effect of the anti-tumoral immune response in glioma. The MΦ inside the tumor mass are associated with multiple phenomena that include IR resistance and enrichment of the M2 MΦ after IR is able to facilitate glioblastoma multiforme (GBM) recurrence. Reviews on the role of cranial IR-induced peripheral and brain-engrafting macrophages (BeMΦ) in glioma are lacking. Specifically, most studies on peripheral, intrinsic as well as beMΦ on IR focus on WHO grade III and IV. Thus, this review precisely focuses primary on WHO grade III as well as IV gliomas.

Performance of Body Adiposity Index and Relative Fat Mass in Predicting Bioelectric Impedance Analysis-Derived Body Fat Percentage: A Cross-Sectional Study among Patients with Type 2 Diabetes in the Ho Municipality, Ghana.

Objective: The study sought to determine the diagnostic accuracy of body adiposity index (BAI) and relative fat mass (RFM) to predict BIA-derived BFP among patients with type 2 diabetes in the Ho municipality. Materials and Method. This hospital-based cross-sectional study involved 236 patients with type 2 diabetes. Demographic data, including age and gender were obtained. Height, waist circumference (WC), and hip circumference (HC) were measured using standard methods. BFP was estimated on a bioelectrical impedance analysis (BIA) scale. The validity of BAI and RFM as alternative estimates for BIA-derived BFP was evaluated based on mean absolute percentage error (MAPE), Passing-Bablok regression, Bland-Altman plots, receiver-operating characteristic curve (ROC), and kappa statistics analyses. A p value less than 0.05 was considered statistically significant. Results: BAI showed systematic bias in estimating BIA-derived BFP in both genders, but this was not evident between RFM and BFP among females (t = -0.62; p = 0.534). While BAI showed "good" predictive accuracy in both genders, RFM exhibited "high" predictive accuracy for BFP (MAPE: 7.13%; 95% CI: 6.27-8.78) among females according to MAPE analysis. From the Bland-Altman plot analysis, the mean difference between RFM and BFP was acceptable among females [0.3 (95% LOA: -10.9 to 11.5)], but both BAI and RFM recorded large limits of agreement and low Lin's concordance correlation coefficient with BFP (Pc < 0.90) in the two gender populations. The optimal cut-off, sensitivity, specificity, and Youden index for RFM were >27.2, 75%, 93.75%, and 0.69, respectively, while those of BAI were >25.65, 80%, 84.37%, and 0.64, respectively, among males. Among females, the values for RFM were >27.26, 92.57%, 72.73%, and 0.65, whereas those of BAI were >29.4, 90.74%, 70.83%, and 0.62, respectively. The accuracy of discriminating between BFP levels was higher among females [BAI (AUC: 0.93) and RFM (AUC: 0.90)] compared to males [BAI (AUC: 0.86) and RFM (AUC: 0.88)]. Conclusion: RFM had a better predictive accuracy of BIA-derived BFP in females. However, both RFM and BAI failed as valid estimates for BFP. Furthermore, gender-specific performance in the discrimination of BFP levels for RFM and BAI was observed.

Placental lesions and differential expression of pro-and anti-angiogenic growth mediators and oxidative DNA damage marker in placentae of Ghanaian suboptimal and optimal health status pregnant women who later developed preeclampsia.

BACKGROUND: Angiogenic growth mediators (AGMs) and oxidative stress (OS) both play essential roles in normal placental vascular development and as such, placental alterations in these factors contribute to pre-eclampsia (PE). Suboptimal health status (SHS), an intermediate between health and disease, has been associated with imbalanced AGMs and OS biomarkers. Thus, SHS pregnant women may be at increased risk of developing PE and may present abnormal placental alteration and expression of AGMs and OS compared to optimal health status (OHS) pregnant women. We examined the histopathological morphology, immunohistochemical expression of AGMs antibodies and oxidative DNA damage marker in the placentae of SHS and OHS pregnant women who developed early-onset PE (EO-PE) and late-onset (LO-PE) compared to normotensive pregnancy (NTN-P). METHODS: This nested case-control study recruited 593 singleton normotensive pregnant women at baseline (10-20 weeks gestation) from the Ghanaian Suboptimal Health Status Cohort Study (GHOACS) undertaken at the Komfo Anokye Teaching Hospital, Ghana. Socio-demographic, clinical and obstetrics data were collected, and a validated SHS questionnaire-25 (SHSQ-25) was used in classifying participants into SHS (n = 297) and OHS (n = 296). Participants were followed until the time of PE diagnosis and delivery (32-42 weeks gestation). Blood samples were collected at the two-time points and were assayed for AGMs; soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PIGF), vascular endothelial growth factor-A (VEGF-A), and soluble endoglin (sEng), and OS biomarkers; 8-hydroxydeoxyguanosine (8-OHdG), 8-epiprostaglandinF2-alpha (8- epi-PGF2α) and total antioxidant capacity (TAC) using ELISA. Placental samples were collected for histopathological and immunohistochemical analysis. RESULTS: Of the 593 pregnant women, 498 comprising 248 SHS and 250 OHS women returned for delivery and were included in the final analysis. Of the 248 SHS women, 56, 97 and 95 developed EO-PE, LO-PE and NTN-P, respectively, whereas 14, 30 and 206 of the 250 OHS mothers developed EO-PE, LO-PE and NTN-P, respectively. At baseline, SHS_NTN pregnant women had a significant imbalance in AGMs and OS biomarkers compared to OHS_NTN pregnant women (p<0.0001). At the time of PE diagnosis, SHS_NTN-P women who developed EO-PE, LO-PE, and NTN-P had lower serum levels of P1GF, VEGF-A and TAC and correspondingly higher levels of sEng, sFlt-1, 8-epiPGF2α, and 8-OHdG than OHS-NTN-P women who developed EO-PE and LO-PE, NTN-P (p<0.0001). A reduced placental size, increased foetal/placental weight ratio, and a significantly higher proportion of fibrinoid necrosis, infarction, villous fibrin, syncytial knots, calcification, chorangiosis, tunica media/vascular wall hypertrophy and chorioamnionitis was associated with the SHS group who developed PE (EO-PE>LO-PE) more than OHS groups who developed PE (EO-PE>LO-PE) when all were compared to NTN-P (p<0.0001). The intensity of antibody expression of PIGF and VEGF-A were significantly reduced, whereas Flt-1, Eng and 8-OHdG were significantly increased in placentae from SHS-pregnant women who developed EO-PE>LO-PE more than OHS- pregnant women who developed EO-PE>LO-PE when all were compared to NTN-P (p<0.0001). CONCLUSION: Increased lesions, oxidative DNA damage, and imbalanced expression between pro-and anti-AGMs are associated more with SHS-embodied PE placentae rather than OHS-embodied PE subtypes, thus potentially allowing differential evaluation of PE.

Crude extracts from Allium cepa skin and Sorghum bicolor seed can provide as non-toxic and eco-friendly cytoplasmic stains.

INTRODUCTION: Staining is an important histological process; however, the use of non-toxic and environmentally friendly products is generally required. We explored the staining quality of two natural plants, Allium cepa skin and Sorghum bicolor seed extract on the cytoplasm. MATERIALS AND METHODS: Distilled water at 37 °C and 1% acid-ethanol were respectively used to extract the dyes from Allium cepa skin and Sorghum bicolor seed. RESULT: The application of these two dyes on rodent tissue showed an excellent cytoplasmic histomorphology. CONCLUSION: Allium cepa skin and Sorghum bicolor seed extracts are good cytoplasmic dyes when used as counterstain for haematoxylin.

Haematological Profile of Adults with Malaria Parasitaemia Visiting the Volta Regional Hospital, Ghana.

BACKGROUND: Malaria is known to cause severe health consequences due to its marked effects and alteration on the haematological parameters of infected individuals. This study evaluated the haematological profile of adult individuals infected with the malaria parasite. METHODS: A retrospective study was conducted using archived data of malaria positive cases from January 2017 to March 15, 2019. Data retrieved included subjects' demographics, malaria parasite count, malaria parasite species, and full blood count parameters. A total of 236 malaria positive subjects were included in the study. RESULTS: The study showed that more females were infected with the malaria parasite than males (69.07% and 30.93%, respectively). A total of 87.3% of the study population were infected with Plasmodium falciparum as compared to 12.7% infected with Plasmodium malariae. The commonest haematological abnormalities that were seen in this study were lymphopenia (56.78%), anaemia (55.51%), thrombocytopenia (47.46%), eosinopenia (45.76%), neutropenia (29.24%), monocytosis (21.19%), and leucocytosis (17.37%) in the infected subjects. The mean platelet count of P. falciparum-infected subjects was decreased as compared to the mean platelet count of P. malariae-infected subjects. There was a significant (P value <0.05) decrease in the number of platelet count with every unit increase in parasite density. CONCLUSION: Study participants infected with malaria demonstrated vital changes in haematological parameters with anaemia, thrombocytopenia, lymphopenia, monocytosis, and eosinopenia being the most important predictors of malaria infection especially with P. falciparum species.P. falciparum-infected subjects was decreased as compared to the mean platelet count of.

Renal abnormalities among children with sickle cell conditions in highly resource-limited setting in Ghana.

Sickle cell disease (SCD) is associated with progressive multi-organ failure especially, the brain and kidney and leads to high morbidity and mortality rate. The aim of this study was to determine the prevalence of renal abnormalities among children with SCD. This cross-sectional study recruited 212 sickling positive patients comprising of 96 Hb AS, 48 Hb SC, and 68 Hb SS phenotypes from the Pediatric Unit of Wassa Akropong Government Hospital, Wassa Akropong, Ghana. Early morning urine and venous blood samples were collected from each participant. Urinalysis was conducted and serum urea and creatinine levels were estimated. Estimate glomerular filtration rate (eGFR) was calculated using the Swartz equation. Classification of chronic kidney disease (CKD) was based on 'The Kidney Disease: Improving Global Outcomes (KIDIGO)' criteria. The mean age of the children were 7.90 years. Serum creatinine (p = 0.0310) and urea (p<0.0001) levels were significantly higher among Hb AS participants compared with Hb SS phenotype. The prevalent indicators of renal abnormalities were proteinuria (26.4%), urine granular cast (5.6%) and CKD (39.6%). Proteinuria, urine granular cast and CKD were most prevalent among Hb SS (47.1%, 11.8% and 73.5% respectively) compared with Hb SC (41.7%, 8.3%, and 45.8% respectively) and Hb AS (4.2%, 0.0%, and 14.5%) phenotypes, respectively. Sickle cell conditions were significantly associated with proteinuria (p<0.0001) and CKD (p = 0.0378). Children with Hb SS [aOR = 5.04, 95% CI (2.47-10.3); p<0.0001] and Hb SC [aOR = 3.14 95% CI (1.39-7.01); p = 0.0174] were at increased odds of developing CKD after adjusting for age, BMI and gender. Proteinuria and CKD are associated with sickle cell disease (Hb SC and Hb SS). Renal function should be routinely monitored for children with SCD.

Anti-anaphylactic effects of Trichilia monadelpha (Thonn.) J. J. De Wilde extracts on rodent models of anaphylaxis.

Effects of petroleum ether and ethanolic extracts of Trichilia monadelpha stem bark (PEE and EAE) on compound 48/80-induced systemic and passive anaphylaxis were determined. Survival rate, extravasation, degranulation of mast cells, and secretion of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured after pre-treatment with extracts (10-100 mg/kg) and disodium chromoglycate (2.5-250 µg/kg) and induction of anaphylaxis in C57BL/6 mice or Sprague-Dawley rats with compound 48/80. Histopathological assessments were made from skin biopsies of rats. Data was analyzed by Kaplan-Meier Survival Log-Rank Analysis, or One-way ANOVA and Holm-Sidak's post hoc test. PEE and EAE inhibited (P ≤ 0.0001) tremors in systemic anaphylaxis passive cutaneous anaphylactic reactions and extravasation, stabilized or prevented (P ≤ 0.001-0.0001) mast cell degranulation, and inhibited (P ≤ 0.001-0.0001) TNF-α and IL-6 secretion. Per the findings, PEE and EAE of T. monadelpha have exhibited substantial anti-anaphylactic and anti-inflammatory property (with PEE performing better) which substantiates its use traditionally in management of allergies and other inflammatory disorders.

Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits.

AIM: To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE) on endotoxin-induced uveitis in New Zealand white rabbits. METHODS: Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS) -induced uveitic rabbits treated orally with HIE (30-300 mg/kg), prednisolone (30 mg/kg), or normal saline (10 mL/kg). The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and monocyte chemmoattrant protein-1 (MCP-1) in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed. RESULTS: The extract and prednisolone-treatment significantly reduced (P≤0.001) both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits) and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001). Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells. CONCLUSION: The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators.

The Claim of Anti-Cataract Potential of Heliotropium indicum: A Myth or Reality?

INTRODUCTION: Heliotropium indicum has several uses in traditional medicine attributable to its numerous bioactive compounds. It is used as a traditional remedy for cataracts in Ghana without any scientific verification. This study aimed at verifying the anti-cataract properties of an aqueous whole plant extract of H. indicum. METHODS: The effect (cataract score) of 30, 100, and 300 mg kg(-1) extract (bid for 21 days, per os) on the development of 30 µmol kg(-1) sodium selenite-induced cataract in 10-day-old rat pups was investigated. Soluble lens proteins alpha A and alpha B crystallins, total lens protein, total lens glutathione, and aquaporin 0 in enucleated lens homogenates were determined spectrophotometrically using commercially available kits. Histopathological studies on the lenses were also performed. The 2,2-diphenyl-1-picrylhydrazyl scavenging effect and linoleic acid autoxidation (antioxidant properties) of the extract (0.1-3.0 mg ml(-1)), compared to n-propyl gallate, were ascertained using standard procedures. RESULTS: Cataract scores showed that the extract, at all dose levels, significantly alleviated selenite-induced cataracts (P ≤ 0.001). Markers of lens transparency (aquaporin 0, alpha A and B crystallins), as well as total lens proteins and lens glutathione levels, were significantly preserved (P ≤ 0.01-0.001). The extract exhibited activity relevant for scavenging free radicals and inhibition of lipid peroxidation. Epithelial and lens fiber integrity in the histopathological assessment were maintained with HIE treatment. CONCLUSION: The aqueous whole plant extract of H. indicum significantly inhibited the development of cataracts in rats via multiple mechanisms.