Physiological and environmental factors affecting cancer risk and prognosis in obesity.

Obesity results from a chronic excessive accumulation of adipose tissue due to a long-term imbalance between energy intake and expenditure. Available epidemiological and clinical data strongly support the links between obesity and certain cancers. Emerging clinical and experimental findings have improved our understanding of the roles of key players in obesity-associated carcinogenesis such as age, sex (menopause), genetic and epigenetic factors, gut microbiota and metabolic factors, body shape trajectory over life, dietary habits, and general lifestyle. It is now widely accepted that the cancer-obesity relationship depends on the site of cancer, the systemic inflammatory status, and micro environmental parameters such as levels of inflammation and oxidative stress in transforming tissues. We hereby review recent advances in our understanding of cancer risk and prognosis in obesity with respect to these players. We highlight how the lack of their consideration contributed to the controversy over the link between obesity and cancer in early epidemiological studies. Finally, the lessons and challenges of interventions for weight loss and better cancer prognosis, and the mechanisms of weight gain in survivors are also discussed.

Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential.

The tumor microenvironment fuels tumorigenesis and induces the development of resistance to anticancer drugs. A growing number of reports support that the tumor microenvironment mediates these deleterious effects partly by overexpressing insulin-like growth factor 1 (IGF-1). IGF-1 is known for its role to support cancer progression and metastasis through the promotion of neovascularization in transforming tissues, and the promotion of the proliferation, maintenance and migration of malignant cells. Anti-IGF therapies showed potent anticancer effects and the ability to suppress cancer resistance to various chemotherapy drugs in in vivo and in vitro preclinical studies. However, high toxicity and resistance to these agents are increasingly being reported in clinical trials. We review data supporting the notion that tumor microenvironment mediates tumorigenesis partly through IGF-1 signaling pathway. We also discuss the therapeutic potential of IGF-1 receptor targeting, with special emphasis on the ability of IGF-R silencing to overcome chemotherapy drug resistance, as well as the challenges for clinical use of anti-IGF-1R therapies.

An Eluate of the Medicinal Plant Garcinia kola Displays Strong Antidiabetic and Neuroprotective Properties in Streptozotocin-Induced Diabetic Mice.

Materials and Methods: G. kola methanolic extract was fractionated using increasingly polar solvents. Fractions were administered to streptozotocin (STZ)-induced diabetic mice until marked motor signs developed in diabetic controls. Fine motor skills indicators were measured in the horizontal grid test (HGT) to confirm the prevention of motor disorders in treated animals. Column chromatography was used to separate the most active fraction, and subfractions were tested in turn in the HGT. Gas chromatography-mass spectrometry (GC-MS) technique was used to assess the components of the most active subfraction. Results: Treatment with ethyl acetate fraction and its fifth eluate (F5) preserved fine motor skills and improved the body weight and blood glucose level. At dose 1.71 mg/kg, F5 kept most parameters comparable to the nondiabetic vehicle group values. GC-MS chromatographic analysis of F5 revealed 36 compounds, the most abundantly expressed (41.8%) being the ß-lactam molecules N-ethyl-2-carbethoxyazetidine (17.8%), N,N-dimethylethanolamine (15%), and isoniacinamide (9%). Conclusions: Our results suggest that subfraction F5 of G. kola extract prevented the development of motor signs and improved disease profile in an STZ-induced mouse model of diabetic encephalopathy. Antidiabetic activity of ß-lactam molecules accounted at least partly for these effects.

Prevalence of precancerous cervical lesions and high-risk human papillomavirus types in Yaounde, Cameroon.

INTRODUCTION: Various Human papillomavirus (HPV) types cause cervical cancer, and represent the primary cause of cancer death in Africa and the second cause of most common cancers in Cameroon. Herein, we determined the prevalence of high-risk HPV types in women and associated cervical cytologic abnormalities in Yaounde, Cameroon. METHODOLOGY: A cross-sectional study targeting HPV-positive women aged 20 and over was conducted between March and June 2020 at the Saint Martin de Porres' Health Centre in Yaounde. HPV tests were performed by PCR for detection of HPVs 16, 18, 33, and 45. The test was performed on 616 women using exfoliated cell specimens; then, we processed on cytological diagnosis with Pap smears on HPV positive specimens. RESULTS: The HPV types tested were detected in 137 participants, of which 38.7% with multiple HPV infections, and the remaining part with single HPV infections of type HPV 16 (28.5%), HPV 18 (17.5%), HPV 33 (10.2%), and HPV 45 (5.1%). Cervical cytologic abnormalities were found in 69.34% of participants including: LSIL (49.63%), HSIL (15.32%), ASC-US (3.66%) and AGC (0.73%). Co-infections with HPV 16 and HPV 18 were significantly associated with HSIL (p = 0.001) lesions, while HPV 45 was more common in participants with normal cytology (p = 0.001). Cervical lesion occurrence was significantly associated with the number of sexual partners (p = 0.02) and history of oral contraceptive pill use (p = 0.001). CONCLUSIONS: Our results suggest that HPV 16 and 18 are predominant in Yaounde, and are associated with more severe precancerous lesions.

Garcinia kola improves cognitive and motor function of a rat model of acute radiation syndrome in the elevated plus maze.

We reported recently that the elevated plus maze is a good tool for evaluating cognitive and motor functional changes in gamma-irradiated rats as a model for new drug evaluation and monitoring. The capacity of Garcinia kola to mitigate radiation-induced brain injury is currently unknown. We therefore assessed the effects of the neuroprotective medicinal plant Garcinia kola, on the cognitive and motor changes in this murine model of acute radiation syndrome. Wistar rats exposed once to an ionizing dose of Tc99m-generated Gamma radiation were treated with an ethyl acetate fraction of methanolic extract of Garcinia kola seeds (content of 100 mg/kg of extract) for 9 weeks. Cognitive and motor function indicators were assessed in the elevated plus maze in these animals and compared with irradiated control groups (vitamin C- and vehicle-treated groups) and the non-irradiated control rats. The irradiated control group displayed cachexia, shaggy and dirty fur, porphyrin deposits around eyes, decreased exploratory activity, reduced social interactions and a loss of thigmotaxis revealed by a marked decrease in rearing episodes and stretch attend posture episodes close to the walls of elevated plus maze closed arm, an increased central platform time, and decreases in open arm time and entries. This group further displayed a decrease in head dips and grooming episodes. Treatment with Garcinia kola, and in a lesser extent vitamin C, significantly prevented the body weight loss (P < 0.001) and mitigated the development of elevated plus maze signs of cognitive and motor affections observed in the irradiated control group (P < 0.05). Altogether, our data suggest for the first time that Garcinia kola seeds have protective properties against the development of cognitive and motor decline in the acute radiation syndrome-like context. Future studies are warranted to characterize the molecular mechanisms and neuronal networks of this action.

Fear and depression during the COVID-19 outbreak in Cameroon: a nation-wide observational study.

BACKGROUND: The COVID-19 pandemic has been associated with significant psychological and social distress worldwide. We investigated fear and depression among adults in Cameroon during different phases of the COVID-19 outbreak. METHODS: An online survey was conducted in Cameroon from June-December 2020 using a structured questionnaire. Socio-demographic data and information regarding COVID-19 history were obtained. Fear and depressive symptoms were assessed using the Fear of COVID-19 score (FCV-19S) and the Patient Health Questionnaire (PHQ-9), respectively. Responses were clustered in weeks to better appreciate their evolution over time. RESULTS: Overall, 7381 responses from all ten regions of Cameroon were analysed (median age: 30 years, 73.3% male). The prevalence of depression (PHQ-9 score ≥ 10) was 8.4%, and that of high fear of COVID-19 (FCV-19S scores ≥19) was 57.4%. These rates were similar across genders, age-groups, and region of residence. While mean weekly PHQ-9 scores remained fairly stable throughout the study period (range: 2.53-3.21; p = 0.101), mean FCV-19S scores were highest during the early weeks but decreased significantly thereafter (from 20.31 to 18.34; p <  0.001). Multivariate analyses revealed that having a postgraduate degree, a history of quarantine, flu-like symptoms during the past 14 days, and higher FCV-19S scores were associated with more severe depressive symptoms, while obtaining COVID-19 information from various sources reduced the odds for depression. CONCLUSION: Depression amidst the COVID-19 crisis is less prevalent in Cameroon than in other countries. Prompt and widespread dissemination of adequate COVID-19 information may reduce the risks for depression by dispelling fear and anxiety among Cameroonians.

Influence of HIV infection on the distribution of high-risk HPV types among women with cervical precancerous lesions in Yaounde, Cameroon.

OBJECTIVES: To characterize high-risk HPV types associated with cervical precancerous lesions in women living in Yaounde, Cameroon, and to determine their distribution with HIV status. METHODS: Women with abnormal pap smears recorded from February 2015 to May 2019 at Saint Martin de Porres' Health Centre, Yaounde, Cameroon, were recruited in this study after obtaining informed consent. Pap smears were collected and re-examined. Human immunodeficiency virus (HIV) serology was determined. HPV16, 18, 33, and 45 were assessed using standard PCR. RESULTS: All included participants (370) were HPV-positive and had either low grade squamous intraepithelial lesions (67.03%) or high grade squamous intraepithelial lesions (31.35%). They were subdivided into HIV-positive (N =102) and HIV-negative (N =268). In the HIV-negative subgroup, we observed 66.04% HPV16-positve, 41.79% HPV18-positve, 21.27% HPV33-positve and 8.21% HPV45-positve. In the HIV-positive subgroup, we observed 22.55% HPV16-positve, 5.88% HPV18-positve, 75.49% HPV33-positve, and 49.02% HPV45-positve. Married HIV-positive participants (47.14 ± 1.19) were older than both their single counterparts (34.94±1.22, P = 0.0008) and HIV-negative participants (41.43 ± 0.79, P = 0.0001). Single HIV-positive women reported higher numbers of miscarriages (P = 0.0023), and had later first sexual intercourse than HIV-negative (P = 0.0079) women. CONCLUSION: Our study suggested differential expressions in high-risk HPV types with HIV status and cervical precancerous lesions and warrants more extensive studies.

COVID-19 Preventive Behaviours in Cameroon: A Six-Month Online National Survey.

Since March 2020, the Cameroonian government implemented nationwide measures to stall COVID-19 transmission. However, little is known about how well these unprecedented measures are being observed as the pandemic evolves. We conducted a six-month online survey to assess the preventive behaviour of Cameroonian adults during the COVID-19 outbreak. A five-point adherence score was constructed based on self-reported observance of the following preventive measures: physical distancing, face mask use, hand hygiene, not touching one's face, and covering the mouth when coughing or sneezing. Predictors of adherence were investigated using ordinal logistic regression models. Of the 7381 responses received from all ten regions, 73.3% were from male respondents and overall mean age was 32.8 ± 10.8 years. Overall mean adherence score was 3.96 ± 1.11 on a scale of 0-5. Mean weekly adherence scores were initially high, but gradually decreased over time accompanied by increasing incidence of COVID-19 during the last study weeks. Predictors for higher adherence included higher age, receiving COVID-19 information from health personnel, and agreeing with the necessity of lockdown measures. Meanwhile, experiencing flu-like symptoms was associated with poor adherence. Continuous observance of preventive measures should be encouraged among Cameroonians in the medium- to long-term to avoid a resurgence in COVID-19 infections.

Anticancer Activity of Combretum fragrans F. Hoffm on Glioblastoma and Prostate Cancer Cell Lines.

BACKGROUND: Cancer incidence has been growing in an alarming rate worldwide and new therapeutics are needed, particularly for intractable and chemoresistant cases. We evaluated the cytotoxic effects of Combretum fragrans F. Hoffm (Combretaceae) on glioblastoma (U87MG and C6) and prostate (PC-3) cancer cell lines. METHODS: The cytotoxic effect of the methanolic extract of the stem bark of Combretum fragrans was assessed using XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Expressions of Akt and ERK1/2 were determined using Western blot technique, while Caspase-3/7 kits were used to evaluate caspase-3/7 activity. RESULTS: C. fragrans extract inhibited the proliferation of U87 (IC50 = 20.13 µg/mL), C6 (IC50 = 12.17 µg/mL), and PC-3 (IC50 = 11.50 µg/mL) cells. Treatment with the extract resulted in lower levels (p < 0.001) of phospho-ERK1/2 and phospho-Akt in U87 cells, and instead, higher levels of phospho-ERK1/2 (p < 0.001) in C6 and PC-3 cells. An increase in caspase-3/7 activity was observed, mainly after 24 hours of treatment, indicating the activation of apoptotic processes. CONCLUSION: Altogether, these results suggest that C. fragrans have potent anticancer properties. This plant should be further investigated for developing new anticancer drugs.

Hypolipidemic and anti-atherosclerogenic effects of aqueous extract of Ipomoea batatas leaves in diet-induced hypercholesterolemic rats.

OBJECTIVE: Ipomoea batatas (L.) Lam. is a food plant used in African traditional medicine to treat cardiovascular diseases and related conditions. We assessed the hypolipidemic and anti-atherosclerogenic properties of the aqueous extract of I. batatas leaves in a rat model of diet-induced hypercholesterolemia. METHODS: Hypercholesterolemia was induced in male Wistar rats by exclusive feeding with a cholesterol-enriched (1%) standard diet for four weeks. Then, rats were treated once daily (per os) with I. batatas extract at doses of 400, 500 and 600 mg/kg or with atorvastatin (2 mg/kg), for four weeks. Following treatment, animals were observed for another four weeks and then sacrificed. Aortas were excised and processed for histopathological studies, and blood glucose level and lipid profile were measured. RESULTS: Hypercholesterolemic animals experienced a 21.5% faster increase in body weight, significant increases in blood glucose and blood lipids (148.94% triglycerides, 196.97% high-density lipoprotein cholesterol, 773.04% low-density lipoprotein cholesterol, 148.93% very low-density lipoprotein cholesterol and 210.42% total cholesterol), and increases in aorta thickness and atherosclerotic plaque sizes compared to rats fed standard diet. Treatment of hypercholesterolemic rats with the extract mitigated these alterations and restored blood glucose and blood lipid levels to normocholesterolemic values. CONCLUSION: Our findings suggest that I. batatas leaves have hypolipidemic and anti-atherosclerogenic properties and justify their use in traditional medicine.

Tumor Microenvironment Uses a Reversible Reprogramming of Mesenchymal Stromal Cells to Mediate Pro-tumorigenic Effects.

The role of mesenchymal stromal cells (MSCs) in the tumor microenvironment is well described. Available data support that MSCs display anticancer activities, and that their reprogramming by cancer cells in the tumor microenvironment induces their switch toward pro-tumorigenic activities. Here we discuss the recent evidence of pro-tumorigenic effects of stromal cells, in particular (i) MSC support to cancer cells through the metabolic reprogramming necessary to maintain their malignant behavior and stemness, and (ii) MSC role in cancer cell immunosenescence and in the establishment and maintenance of immunosuppression in the tumor microenvironment. We also discuss the mechanisms of tumor microenvironment mediated reprogramming of MSCs, including the effects of hypoxia, tumor stiffness, cancer-promoting cells, and tumor extracellular matrix. Finally, we summarize the emerging strategies for reprogramming tumor MSCs to reactivate anticancer functions of these stromal cells.

Evaluation of metabolic, antioxidant and anti-inflammatory effects of Garcinia kola on diabetic rats.

Garcinia kola (G. kola), is a plant characterized by its hypoglycemic properties. We recently reported our findings on the extracts of G. kola, in which we found that it prevented the loss of inflammation-sensible neuronal populations in streptozotocin (STZ)-induced rat models of type 1 diabetes mellitus (T1DM). In the present study we assessed the effect of G. kola bioactive compounds extracted successively with water, hexane, methylene chloride, ethyl acetate, and butanol. through analyzing biochemical markers of oxidative stress, inflammation, and metabolic function in STZ-induced diabetic animals. Animals made diabetic by a single injection with STZ (60 mg/kg, i.p.), were treated daily with either vehicle solution, insulin, or G. kola extracts and its fractions from the first to the 6th-week post-injection. Biochemical markers; glucose, insulin, C-peptide, neuron-specific enolase (NSE), creatinine kinase, glutathione peroxidase, malondialdehyde (MDA), resistin, soluble E-selectin (SE-Selectin), and C-reactive proteins (CRP) levels in the sera were determined in the study groups. A marked increase in blood glucose (209.26% of baseline value), and a decrease in body weight (-12.37%) were observed in diabetic control animals but not in animals treated with either insulin or G. kola extracts and its fractions. The sub-fraction F5, G. kola ethyl acetate had the highest bioactive activities, with a maintenance of blood sugar, malondialdehyde, C-peptide, E-selectin, C-reactive protein (CRP) and neuron-specific enolase (NSE) to levels and responses comparable to healthy non-diabetic vehicle group and the positive control diabetic insulin-treated group. Our findings suggest that G. kola may have a strong therapeutic potential against T1DM and its microvascular complications.

Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects.

After more than a decade of controversy on the role of stromal cells in the tumor microenvironment, the emerging data shed light on pro-tumorigenic and potential anti-cancer factors, as well as on the roots of the discrepancies. We discuss the pro-tumorigenic effects of stromal cells, considering the effects of tumor drivers like hypoxia and tumor stiffness on these cells, as well as stromal cell-mediated adiposity and immunosuppression in the tumor microenvironment, and cancer initiating cells' cellular senescence and adaptive metabolism. We summarize the emerging data supporting stromal cell therapeutic potential in cancer, discuss the possibility to reprogram stromal cells of the tumor microenvironment for anti-cancer effects, and explore some causes of discrepancies on the roles of stromal cells in cancer in the available literature.

Effect of Aqueous Extract of Adansonia digitata Stem Bark on the Development of Hypertension in L-NAME-Induced Hypertensive Rat Model.

BACKGROUND: Adansonia digitata is a plant used against cardiovascular disorders in African folk medicine. We assessed the effects of the aqueous extract of its stem bark on the development of hypertension in L-NAME-induced hypertensive rats. METHODS: The animals were administered L-NAME once daily for 3 weeks (25 mg/kg, i.p.), concomitantly with aqueous extract of A. digitata stem bark (100 and 200 mg/kg, p.o.) or captopril (20 mg/kg, p.o.). Then, hemodynamic and electrocardiographic parameters, oxidative stress markers, and the lipid profile were assessed in the blood and heart, aorta, and kidney homogenates, and histopathological analyses were performed. RESULTS: L-NAME-induced hypertensive control animals, but not the animals concomitantly treated with A. digitata extract, displayed increases in the mean arterial blood pressure (21.64% difference, p < 0.001, vs. dose 200 mg/kg), systolic arterial blood pressure (21.33%, p < 0.001), and the diastolic arterial blood pressure (21.84%, p < 0.001). In addition, hypertensive control animals displayed (i) increases in serum triglycerides, total cholesterol, LDL, and creatinine levels, malondialdehyde and transaminase activities, and atherogenic index; (ii) decreases in serum HDL, catalase, reduced glutathione, and nitric oxide; and (iii) aorta wall thickening, inflammatory cell infiltration, and cell loss in the cardiac muscle and renal tissues. As captopril, the extract prevented hypertension-like changes in lipid profile, cardiac, hepatic, and renal affection indicators, and oxidative stress markers. CONCLUSION: Our findings suggest that the extract of A. digitata has antihypertensive and antioxidant effects in L-NAME-induced hypertension rat models. These effects partly justify the traditional medicine use against cardiovascular disorders.

The Actigraphy Sleep Score: A New Biomarker for Diagnosis, Disease Staging, and Monitoring in Human African Trypanosomiasis.

Human African trypanosomiasis (HAT) remains a serious public health problem with diagnostic and treatment challenges in many African countries. The absence of a gold-standard biomarker has been a major difficulty for accurate disease staging and treatment follow-up. We therefore attempted to develop a simple, affordable, and noninvasive biomarker for HAT diagnosis and staging. Simultaneous actigraphy and polysomnography as well as cerebrospinal fluid (CSF) white blood cell (WBC) count, trypanosome presence, and C-X-C motif ligand (CXCL)-10 cytokine levels were performed in 20 HAT patients and nine healthy individuals (controls) using standard procedures. The International HIV Dementia Scale (IHDS) was scored in some patients as a surrogate for clinical assessment. From actigraphic parameters, we developed a novel sleep score and used it to determine correlations with other HAT markers, and compared their performance in differentiating between patients and controls and between HAT stages. The novel actigraphy sleep score (ASS) had the following ranges: 0-25 (healthy controls), 67-103 (HAT stage I), 111-126 (HAT intermediate), and 133-250 (HAT stage II). Compared with controls, stage I patients displayed a 7-fold increase in the ASS (P < 0.01), intermediate stage patients a 10-fold increase (P < 0.001), and HAT stage II patients an almost 20-fold increase (P < 0.001). CXCL-10 showed high interindividual differences. White blood cell counts were only marked in HAT stage II patients with a high interindividual variability. The International HIV Dementia Scale score negatively correlated with the ASS. We report the development and better performance of a new biomarker, ASS, for HAT diagnosis, disease staging, and monitoring that needs to be confirmed in large cohort studies.

Garcinia kola seeds may prevent cognitive and motor dysfunctions in a type 1 diabetes mellitus rat model partly by mitigating neuroinflammation.

Background We reported recently that extracts of seeds of Garcinia kola, a plant with established hypoglycemic properties, prevented the loss of inflammation-sensible neuronal populations like Purkinje cells in a rat model of type 1 diabetes mellitus (T1DM). Here, we assessed G. kola extract ability to prevent the early cognitive and motor dysfunctions observed in this model. Methods Rats made diabetic by single injection of streptozotocin were treated daily with either vehicle solution (diabetic control group), insulin, or G. kola extract from the first to the 6th week post-injection. Then, cognitive and motor functions were assessed using holeboard and vertical pole behavioral tests, and animals were sacrificed. Brains were dissected out, cut, and processed for Nissl staining and immunohistochemistry. Results Hyperglycemia (209.26 %), body weight loss (-12.37 %), and T1DM-like cognitive and motor dysfunctions revealed behavioral tests in diabetic control animals were not observed in insulin and extract-treated animals. Similar, expressions of inflammation markers tumor necrosis factor (TNF), iba1 (CD68), and Glial fibrillary acidic protein (GFAP), as well as decreases of neuronal density in regions involved in cognitive and motor functions (-49.56 % motor cortex, -33.24 % medial septal nucleus, -41.8 % /-37.34 % cerebellar Purkinje /granular cell layers) were observed in diabetic controls but not in animals treated with insulin or G. kola. Conclusions Our results indicate that T1DM-like functional alterations are mediated, at least partly, by neuroinflammation and neuronal loss in this model. The prevention of the development of such alterations by early treatment with G. kola confirms the neuroprotective properties of the plant and warrant further mechanistic studies, considering the potential for human disease.

Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

BACKGROUND: Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease. METHODOLOGY/PRINCIPAL FINDINGS: The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness. CONCLUSIONS/SIGNIFICANCE: The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis.

Evaluation of the safety of conventional lighting replacement by artificial daylight.

BACKGROUND: Short morning exposure to high illuminance visible electromagnetic radiations termed as artificial daylight is beneficial for the mental health of people living in geographical areas with important seasonal changes in daylight illuminance. However, the commercial success of high illuminance light sources has raised the question of the safety of long hour exposure. METHODS: We have investigated the effect of the replacement of natural daylight by artificial daylight in Swiss mice raised under natural lighting conditions. Mice were monitored for neurotoxicity and general health changes. They were submitted to a battery of conventional tests for mood, motor and cognitive functions' assessment on exposure day (ED) 14 and ED20. Following sacrifice on ED21 due to marked signs of neurotoxicity, the expression of markers of inflammation and apoptosis was assessed in the entorhinal cortex and neurons were estimated in the hippocampal formation. RESULTS: Signs of severe cognitive and motor impairments, mood disorders, and hepatotoxicity were observed in animals exposed to artificial daylight on ED20, unlike on ED14 and unlike groups exposed to natural daylight or conventional lighting. Activated microglia and astrocytes were observed in the entorhinal cortex, as well as dead and dying neurons. Neuronal counts revealed massive neuronal loss in the hippocampal formation. CONCLUSIONS: These results suggest that long hour exposure to high illuminance visible electromagnetic radiations induced severe alterations in brain function and general health in mice partly mediated by damages to the neocortex-entorhinal cortex-hippocampus axis. These findings raise caution over long hour use of high illuminance artificial light.

Garcinia kola aqueous suspension prevents cerebellar neurodegeneration in long-term diabetic rat - a type 1 diabetes mellitus model.

ETHNOPHARMACOLOGICAL RELEVANCE: The development of compounds able to improve metabolic syndrome and mitigate complications caused by inappropriate glycemic control in type 1 diabetes mellitus is challenging. The medicinal plant with established hypoglycemic properties Garcinia kola Heckel might have the potential to mitigate diabetes mellitus metabolic syndrome and complications. AIM OF THE STUDY: We have investigated the neuroprotective properties of a suspension of G. kola seeds in long-term type 1 diabetes mellitus rat model. MATERIALS AND METHODS: Wistar rats, made diabetic by single injection of streptozotocin were monitored for 8 months. Then, they were administered with distilled water or G. kola oral aqueous suspension daily for 30 days. Body weight and glycemia were determined before and after treatment. After sacrifice, cerebella were dissected out and processed for stereological quantification of Purkinje cells. Histopathological and immunohistochemical analyses of markers of neuroinflammation and neurodegeneration were performed. RESULTS: Purkinje cell counts were significantly increased, and histopathological signs of apoptosis and neuroinflammation decreased, in diabetic animals treated with G. kola compared to diabetic rats given distilled water. Glycemia was also markedly improved and body weight restored to non-diabetic control values, following G. kola treatment. CONCLUSIONS: These results suggest that G. kola treatment improved the general condition of long-term diabetic rats and protected Purkinje cells partly by improving the systemic glycemia and mitigating neuroinflammation.

Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes.

BACKGROUND: The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications. METHODOLOGY: Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM) periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses. PRINCIPAL FINDINGS: Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion. CONCLUSION: These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging.