Prognostic Significance of Nuclear Factor Kappa B (p65) among Breast Cancer Patients in Cape Coast Teaching Hospital.

Breast cancer is the most prevalent cancer among African women, with high mortality rates in Ghana. Nuclear factor kappa B (NF-kB) has been associated with tumor progression in breast cancer. However, its clinical validation is controversial and understudied with no known published data on NF-kB (p65) among breast cancer patients in Ghana and other African countries. This study assessed the prognostic significance of NF-kB (p65) expression and its association with various clinicopathological features in breast cancer patients. Ninety formalin-fixed breast cancer tissues and 15 normal breast tissues were used to determine the expression of NF-kB (p65) using immunohistochemistry. We explored the correlation between expression of NF-kB (p65) and clinicopathological features. NF-kB (p65) was expressed in 86.7% of breast cancer tissues. There was a significant relationship between NF-kB (p65) expression and tumor grade, proliferation index (Ki67), and molecular subtype. High NF-kB (p65) expression in tumor grade 3 was about 10 times that of grade 1 (54.2% vs. 5.1%), and Ki67 > 20 was 79.7% compared to 20.3% for Ki67 ≤ 20. Patients with triple-negative breast cancer (TNBC) had 49.1% overexpression of NF-kB (p65) compared to 17%, 25.4%, and 8.5% for luminal A, luminal B, and HER2 cases, respectively. This study demonstrates that NF-kB (p65) was highly expressed among breast cancer patients at Cape Coast Teaching Hospital, Ghana, especially in TNBC. NF-kB (p65) could serve as a biomarker for cancer stage, progression, prognosis and as a therapeutic target.

Prognostic Worth of Nrf2/BACH1/HO-1 Protein Expression in the Development of Breast Cancer.

OBJECTIVES: Nrf2/BACH1/HO-1 proteins have been implicated in the development and progression of tumors. However, their clinical relevance in breast cancer remains unclear and understudied. This study evaluated Nrf2/BACH1/HO-1 protein expression and its relationship with age, tumor grade, tumor stage, TNM, ER, PR, HER2, and histologic type. METHODS: 114 female breast cancer and 30 noncancerous tissues were evaluated for Nrf2/BACH1/HO-1 protein expression using immunohistochemistry and Western blot. The relationships between the expression and clinicopathologic factors were assessed using the χ2 test. RESULTS: 74% of the cancerous samples had high Nrf2 protein expression, and 26% of them had low Nrf2 protein expression. Regarding the non-cancer samples, 43% had high Nrf2 protein expression and 57% had low Nrf2 protein expression (p < 0.002). 39% of the cancerous samples had high BACH1 protein expression, and 61% had low BACH1 protein expression. For the non-cancer samples, 80% had high BACH1 protein expression and 20% had low BACH1 protein expression (p < 0.031). 67% of the cancerous samples had high HO-1 protein expression, and 33% had low HO-1 protein expression. However, for the non-cancer samples, 17% of them had high HO-1 protein expression and 83% had low HO-1 protein expression (p < 0.001). The expression of Nrf2 and HO-1 significantly correlated with tumor grade, while BACH1 was significantly associated with tumor stage (p < 0.05). CONCLUSION: Nrf2, BACH1, and HO-1 could be explored as a biomarker for cancer stage, progression, and prognosis.

Efficacy of combined antioxidant therapy in male subfertility-A systematic review and meta-analysis.

Antioxidant therapy is a potentially promising approach to improve clinical outcomes for couples undergoing assisted reproduction techniques long-term. The review aims to (a) collate evidence for the effectiveness of combined oral antioxidant supplementation, including a head-to-head comparison in the treatment of male subfertility, and (b) investigate whether other intervention features, including duration, specific combinations, or dosage affect clinical outcomes in this population. Randomized controlled trials (RCTs) that examined the effectiveness of combined antioxidants on male subfertility, electronic databases including PubMed, Embase, CINAHL, PSYCHINFO, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched. We also searched for unpublished data and references of identified articles. Two reviewers screened eligible studies according to pre-defined criteria and relevant data extracted. The Jadad scale assessed the quality of studies. The study used RevMan version 5.4.1 Meta-analysis software to analyze the effect of combination antioxidants for each outcome measure. Metadata was presented as relative risks for dichotomous outcomes and as standardized mean differences (or mean differences) for continuous outcomes. The systematic review and meta-analysis aimed to report available evidence of whether combination antioxidant is effective and safe in sub-fertile men undergoing assisted reproductive techniques. Also, this review highlighted whether any specific oral antioxidant combinations, dosage, or duration of therapy have a major influence on the clinical outcomes.

The Effect of Active Release Technique® on Clinician and Patient-Reported Outcomes: A Systematic Review.

CONTEXT: Active Release Technique® (ART®) is a manual therapy used for soft tissue-related issues, commonly used to lengthen structures in a shortened position and to restore motion of soft tissues. OBJECTIVE: The purpose of this systematic review was to collect, appraise, and summarize the available literature, evaluating the effects of ART® on pain, range of motion (ROM), and disability. EVIDENCE ACQUISITION: Electronic databases (PubMed, EBSCOhost, MEDLINE, SPORTDiscus, and CINAHL) were searched from 2000 to November 2020. The search was completed using a combination of key words related to ART®, rehabilitation, and outcomes. Search limits were full-text publications written in English. Inclusion criteria required that studies evaluated outcomes using ART® for rehabilitation, were peer reviewed, and included human participants without catastrophic conditions or injuries. The modified Downs and Black checklist for nonrandomized studies was used to assess methodological quality of identified studies by 2 independent reviewers, average scores were calculated. The level of evidence was assessed using the strength of recommendation taxonomy. EVIDENCE SYNTHESIS: Nine studies were inculded in this review. The average methodological quality of the studies was 12/15 and ranged from 10 to 14, with the most common methodological quality item missed being the blinding of researchers collecting outcomes. Six studies that assessed pain found significant improvements in participants' pain levels. Six studies that assessed ROM found significant improvement in participants' ROM. Two studies that assessed disability found significant improvement in disability. CONCLUSION: Evidence suggests that ART® may be beneficial in improving pain, ROM, and disability. This review found that ART® positively impacted patient outcomes and may be a viable treatment option for clinicians treating musculoskeletal conditions. However, further research is necessary to determine optimal dosage and long-term effects of ART® on these patient outcomes.

Effect of hookworm infection and anthelmintic treatment on naturally acquired antibody responses against the GMZ2 malaria vaccine candidate and constituent antigens.

BACKGROUND: Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens. METHODS: This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment. RESULTS: Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment. CONCLUSION: Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.

Expression of RAS and RAB interactor 1 (RIN1) in head and neck tumors at selected hospital in Ghana.

BACKGROUND: Head and neck tumors (HNT) are tumors of the paranasal sinuses, the salivary glands and the upper aerodigestive tract. RIN1 is a Ras effector protein regulating epithelial cell properties and has been implicated in a number of cancers. METHOD: The aim of this study was to investigate the expression of RIN1 in head and neck tumors. RIN1 expression was assessed using quantitative real-time PCR (qRT-PCR) and immunohistochemical staining on archival head and neck tissue samples between 2014 and 2020. RESULTS: RIN1 expression was low in tissue samples as compared with the normal head and neck tissues. High and low RIN1 levels were compared with ages ≤40, >40 in the head and neck tumors of p-value 0.02. There was a significant difference with p-values of 0.001 when poor and well-moderate malignant tumors were compared. CONCLUSION: Our data suggests that RIN1may play an important role in head and neck tumor progression and that its expression may provide baseline data to facilitate identification of new molecular targeted therapeutics.

Retention of tissue texture change after cervical muscle energy and high velocity low amplitude intervention: implications for treatment intervals.

CONTEXT: When choosing to incorporate osteopathic manipulative treatment (OMT) into a patient's care, the risk-to-benefit ratio, the choice of treatment technique, as well as the frequency of treatments are always taken into consideration. This has been even more important during the COVID-19 pandemic, in which social distancing has been the best preventative measure to decrease exposure. By increasing treatment intervals, one could not only limit possible exposure/spread of viruses but also decrease the overall cost to the system as well as to the individual. This is an expansion of a previous study in which quantifiable changes in cervical hysteresis characteristics post-OMT were documented utilizing a durometer (Ultralign SA201®; Sigma Instruments; Cranberry, PA USA). This study compared two treatment modalities, muscle energy (ME) and high-velocity low-amplitude (HVLA) postcervical treatment. Subjects in this study were allowed to re-enroll, provided that they could be treated utilizing the alternate treatment modality. By allowing repeat subjects, analysis of the data for lasting effects of OMT could be observed. OBJECTIVES: To determine whether a significant change in cervical hysteresis would be observed after each treatment regardless of a short treatment interval. METHODS: A total of 34 subjects were retrospectively noted to be repeat subjects from a larger, 213-subject study. These 34 subjects were repeat participants who were treated with two different direct-treatment modalities 7-10 days apart. Each subject was randomly assigned to receive a single-segmental ME or HVLA treatment technique directed toward a cervical (C) segment (C3-C5 only). Subjects were objectively measured pretreatment in all cervical segments utilizing the Ultralign SA201®, then treated with cervical OMT to a single segment, and finally reassessed at all cervical levels with the Ultralign SA201® posttreatment to assess for change in cervical hysteresis. RESULTS: Statistically significant or suggestive changes (p-values 0.01-0.08) with good clinical effect size (0.30 or greater) were noted in all four components of the Ultralign SA201® at multiple cervical levels after the first treatment, but only one component (frequency) had a statistically significant change after the second treatment (AA cervical level, p-value 0.01) with good clinical effect size (0.45). However, when comparing the post-first-treatment values to the pre-second-treatment values, no statistically significant differences (p-value 0.10 or higher) were observed between them. CONCLUSIONS: Statistically significant changes were noted after the first treatment; however, when comparing cervical hysteresis changes after the first treatment to the cervical hysteresis values prior to the second treatment delivered 7-10 days later, there were no statistically significant or suggestive changes. This data suggest that several post-OMT changes noted after the first treatment were still in effect and may indicate that follow-up visits for direct manipulation may be deferred for a least two weeks.

A Review: Mechanism of Phyllanthus urinaria in Cancers-NF-κB, P13K/AKT, and MAPKs Signaling Activation.

Phyllanthus urinaria has been characterized for its several biological and medicinal effects such as antiviral, antibacterial, anti-inflammatory, anticancer, and immunoregulation. In recent years, Phyllanthus urinaria has demonstrated potential to modulate the activation of critical pathways such as NF-κB, P13K/AKT, and ERK/JNK/P38/MAPKs associated with cell growth, proliferation, metastasis, and apoptotic cell death. To date, there is much evidence indicating that modulation of cellular signaling pathways is a promising approach to consider in drug development and discovery. Thus, therapies that can regulate cancer-related pathways are longed-for in anticancer drug discovery. This review's focus is to provide comprehensive knowledge on the anticancer mechanisms of Phyllanthus urinaria through the regulation of NF-κB, P13K/AKT, and ERK/JNK/P38/MAPKs signaling pathways. Thus, the review summarizes both in vitro and in vivo effects of Phyllanthus urinaria extracts or bioactive constituents with emphasis on tumor cell apoptosis. The literature information was obtained from publications on Google Scholar, PubMed, Web of Science, and EBSCOhost. The key words used in the search were "Phyllanthus" or "Phyllanthus urinaria" and cancer. P. urinaria inhibits cancer cell proliferation via inhibition of NF-κB, P13K/AKT, and MAPKs (ERK, JNK, P38) pathways to induce apoptosis and prevents angiogenesis. It is expected that understanding these fundamental mechanisms may help stimulate additional research to exploit Phyllanthus urinaria and other natural products for the development of novel anticancer therapies in the future.

Ameliorative Effect of Vernonia amygdalina Plant Extract on Heavy Metal-Induced Liver and Kidney Dysfunction in Rats.

Heavy metal toxicity contributes to liver and kidney dysfunction and damage through oxidative stress mechanisms; however, from previous studies, extracts from the Vernonia amygdalina plant have shown to possess potent antioxidant properties. This study was aimed at uncovering the potential ameliorative effects of ethanolic extract from Vernonia amygdalina plant in heavy metal toxicity-induced liver and kidney dysfunction. For this study, 44 Sprague Dawley rats were divided into three groups. The control group received a basal diet and water only while the treatment groups received varied dosages of the heavy metals. The copper (Cu) and lead (Pb) groups had five subgroups. The Cu only and Cu recovery subgroups were administered with 16 mg/kg Cu intraperitoneally daily for 14 days, whereas the Pb only and Pb recovery subgroups were administered with 13 mg/kg Pb intraperitoneally daily for 14 days. Subsequently, the Pb only and Cu only subgroups were sacrificed. The three Pb and Cu treatment subgroups received oral graded doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of the extract for 21 days. The Cu recovery and Pb recovery subgroups were left to recover for 21 days. After histological examinations, the Pb and Cu pretreatment groups showed evidence of focal necrosis accompanied by inflammatory cell infiltrations. The serum levels of liver biomarkers AST, ALT, and GGT, as well as urea and creatinine, were significantly elevated (P=0.01) following copper and lead exposure. Upon posttreatment of the rats with the extract, the physiological levels of the biomarkers were restored and tissue architecture of the organs improved. Thus, the ethanolic extract of Vernonia amygdalina is capable of ameliorating the effects of heavy metal toxicity through potent antioxidative mechanisms.

Prognostic Worth of Epidermal Growth Factor Receptor (EGFR) in Patients with Head and Neck Tumors.

INTRODUCTION: Head and neck tumors (HNT) are tumors that normally occur at the head and neck region of the body. Epidermal growth factor receptor (EGFR) has been found to be highly expressed in breast and other tumors; therefore, there is the need to investigate the level of EGFR expression among patients with head and neck tumors in Ghana. METHOD: The level of EGFR expression was determined in head and neck tumor and control head and neck tissues with quantitative real-time PCR and immunohistochemistry analysis. RESULTS: The level of EGFR expressions was high in tumor tissues than in the control tissues. There was a significant difference of p value 0.025 among the ages >40 and ≤ 40 when the high and low level of EGFR was compared in the head and neck malignant tumor. The area under the curve for the high expression of EGFR among the malignant head and neck tumors was 0.901 with a specificity of 86.4%. CONCLUSION: EGFR can serve as a prognostic marker in monitoring patients with HNT as well as a molecular therapeutic target.

Corrigendum to "Antidiabetic Effect of Young and Old Ethanolic Leaf Extracts of Vernonia amygdalina: A Comparative Study".

[This corrects the article DOI: 10.1155/2016/8252741.].

Antidiabetic Effect of Young and Old Ethanolic Leaf Extracts of Vernonia amygdalina: A Comparative Study.

The young leaves of Vernonia amygdalina are often utilized as vegetable and for medicinal purpose compared to the old leaves. This study was designed to evaluate and compare the antidiabetic effects between ethanolic leaf extracts of old and young V. amygdalina on streptozotocin (STZ) induced diabetic rat for four weeks. Preliminary screening of both young and old ethanolic extracts revealed the presence of the same phytochemicals except flavonoids which was only present in the old V. amygdalina. Difference in antioxidant power between the young and old leaf extracts was statistically significant (p < 0.05). Both leaf extracts produced a significant (p < 0.05) antihyperglycaemic effect. Also results from treated rats revealed increasing effect in some haematological parameters. Similarly, the higher dose (300 mg/kg) of both extracts significantly (p < 0.05) reduced serum ALT, AST, and ALP levels as compared to the diabetic control rats. Results also showed significant (p < 0.05) decrease in LDL-C and VLDL-C in the extract-treated rats with a corresponding increase in HDL-C, as compared to the diabetic control rats. Moreover histopathological analysis revealed ameliorative effect of pathological insults induced by the STZ in the pancreas, liver, and spleen, most significantly the regeneration of the beta cells of the islets of Langerhans in treated rats.

A comparative study of cervical hysteresis characteristics after various osteopathic manipulative treatment (OMT) modalities.

BACKGROUND: Few objective measures have been used to document change in myofascial tissues after OMT. HYPOTHESIS: Paraspinal tissues associated with cervical somatic dysfunction (SD) will demonstrate quantifiable change in myofascial hysteresis characteristics after a given OMT technique but not after a Sham intervention. MATERIALS & METHODS: 240 subjects were palpated for cervical articular SD. A randomly selected intervention (5 OMT techniques or a Sham) was applied to the cervical SD clinically considered to be most severe. A durometer (SA201(®); Sigma Instruments, Cranberry, PA, USA) objectively measured myofascial structures overlying each cervical spinal segment pre- and post- intervention. Using a single consistent piezoelectric impulse, this durometer quantified four hysteresis (tissue texture) characteristics--fixation, mobility, frequency, and motoricity. RESULTS: Baseline changes in median hysteresis values were noted for each OMT technique but not for Sham interventions. Notably, segmental counterstrain OMT resulted in significant motoricity change compared to adjacent segmental myofascial measures (p-value 0.04) along with a suggestive trend in the mobility component (p-value 0.12). CONCLUSION: When comparing treated to untreated cervical segments, the most significant change occurred post-counterstrain OMT with no overall change following Sham. Overall, quantifiable objective change occurs in myofascial tissues post-OMT, in addition to the noted clinical palpable change.