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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks specific targets such as estrogen, progesterone, and HER2 receptors. TNBC affects one in eight women in the United States, making up 15-20% of breast cancer cases. Patients with TNBC can develop resistance to chemotherapy over time, leading to treatment failure. Therefore, finding other options like natural products is necessary for treatment. The advantages of using natural products sourced from plants as anticancer agents are that they are less toxic, more affordable, and have fewer side effects. These products can modulate several cellular processes of the tumor microenvironment, such as proliferation, migration, angiogenesis, cell cycle arrest, and apoptosis. The phosphatidyl inositol 3-kinase (PI3K)-AKT signaling pathway is an important pathway that contributes to the survival and growth of the tumor microenvironment and is associated with these cellular processes. This current study examined the anticancer effects of fucoxanthin, a marine carotenoid isolated from brown seaweed, in the MDA-MB-231 and MDA-MB-468 TNBC cell lines. The methods used in this study include a cytotoxic assay, PI3K-AKT signaling pathway PCR arrays, and Wes analysis. Fucoxanthin (6.25 µM) + TNF-α (50 ng/mL) and TNF-α (50 ng/mL) showed no significant effect on cell viability compared to the control in both MDA-MB-231 and MDA-MB-468 cells after a 24 h treatment period. PI3K-AKT signaling pathway PCR array studies showed that in TNF-α-stimulated (50 ng/mL) MDA-MB-231 and MDA-MB-468 cells, fucoxanthin (6.25 µM) modulated the mRNA expression of 12 genes, including FOXO1 , RASA1 , HRAS , MAPK3 , PDK2 , IRS1 , EIF4EBP1 , EIF4B , PTK2 , TIRAP , RHOA , and ELK1 . Additionally, fucoxanthin significantly downregulated the protein expression of IRS1, EIF4B, and ELK1 in MDA-MB-231 cells, and no change in the protein expression of EIF4B and ELK1 was shown in MDA-MB-468 cells. Fucoxanthin upregulated the protein expression of RHOA in both cell lines. The modulation of the expression of genes and proteins of the PI3K-AKT signaling pathway may elucidate fucoxanthin's effects in cell cycle progression, apoptotic processes, migration, and proliferation, which shows that PI3K-AKT may be the possible molecular mechanism for fucoxanthin's effects. In conclusion, the results obtained in this study elucidate fucoxanthin's molecular mechanisms and indicate that fucoxanthin may be considered a promising candidate for breast cancer-targeted therapy.

The lack of hormone receptors in triple negative breast cancer (TNBC) is associated with the inefficacy of anti-estrogen chemotherapies, leaving fewer options for patient treatment and higher mortality rates. Additionally, as with numerous types of inflammatory breast cancer, infiltration of tumor associated macrophages and other leukocyte sub-populations within the tumor inevitably lead to aggressive, chemo-resistant, metastatic and invasive types of cancer which escape immune surveillance. These processes are orchestrated by the release of potent cytokines, including TNFα, IL-6 and CCL2 from the stroma, tumor and immune cells within the tumor microenvironment. The present study evaluated apigenin modulating effects on the pro-inflammatory activating action of TNFα in TNBC MDA-MB-468 cells, derived from an African American woman. Initially, cell viability was determined to establish an optimal sub-lethal dose of TNFα and apigenin in MDA-MB-468 cells. Subsequently, various treatments effects were evaluated using whole transcriptomic analysis of mRNA and long intergenic non-coding RNA with Affymetrix HuGene-2.1-st human microarrays. Gene level differential expression analysis was conducted on 48,226 genes where TNFα caused significant upregulation of 53 transcripts and downregulation of 11 transcripts. The largest upward differential shift was for CCL2 [+61.86 fold change (FC); false discovery rate (FDR), P<0.0001]; which was down regulated by apigenin (to +10.71 FC vs. Control; FDR P-value <0.001), equivalent to an 83% reduction. Several TNFα deferentially upregulated transcripts were reduced by apigenin, including CXCL10, C3, PGLYRP4, IL22RA2, KMO, IL7R, ROS1, CFB, IKBKe, SLITRK6 (a checkpoint target) and MMP13. Confirmation of CCL2 experimentally induced transcript alterations was corroborated at the protein level by ELISA assays. The high level of CCL2 transcript in the cell line was comparable to that in our previous studies in MDA-MB-231 cells. The differential effects of TNFα were corroborated by ELISA, where the data revealed a >10-fold higher releasing rate of CCL2 in MDA-MB-468 cells compared with in MDA-MB-231 cells, both of which were attenuated by apigenin. The data obtained in the present study demonstrated a high level of CCL2 in MDA-MB-468 cells and a possible therapeutic role for apigenin in downregulating TNFα-mediated processes in these TNBC cells., (Copyright: © Bauer et al.)

Background: Prostate cancer is the second most common cause of mortality. Gallic acid (GA) is a natural polyphenol, and we tested its in-vitro cytotoxicity after 24 h in prostate cancer LNCaP cells., Materials and Methods: GA autoxidation was measured fluorimetrically for H(2)O(2), and O(2)(•-) radicals by chemiluminescence. Intracellular reactive oxygen species (ROS) levels were detected with 2',7'-dichlorodihydrofluorescein diacetate. Cytotoxicity was evaluated by crystal-violet, while apoptosis and mitochondrial membrane potential were determined by flow cytometry. Cytochrome c release was detected by enzyme-linked immunosorbent assay, and caspase-8, -9 and -3 activities were measured calorimetrically., Results: GA autoxidation produced significant levels of H(2)O(2) and O2.-. Increased intracellular ROS levels with GA were reduced by N-acetyl-L-cysteine (NAC) and L-glutathione (GSH). Cells were protected against GA cytotoxicity when pretreated with increasing levels of superoxide dismutase/catalase mixture, NAC, or GSH for 3 h. The number of apoptotic cells increased with GA dose. GA caused mitochondrial potential loss, cytochrome c release, and activation of caspases 3, 8 and 9., Conclusion: The ROS-dependent apoptotic mechanism of GA kills malignant cells effectively; it is likely that GA could be a good anticancer agent.

Diallyl disulfide (DADS), a garlic organosulfur compound, has been researched as a cancer prevention agent; however, the role of DADS in the suppression of cancer initiation in nonneoplastic cells has not been elucidated. To evaluate DADS inhibition of early carcinogenic events, MCF-10A cells were pretreated (PreTx) with DADS followed by the ubiquitous carcinogen benzo(a)pyrene (BaP), or cotreated (CoTx) with DADS and BaP for up to 24 h. The cells were evaluated for changes in cell viability/proliferation, cell cycle, induction of peroxide formation, and DNA damage. BaP induced a statistically significant increase in cell proliferation at 6 h, which was attenuated with DADS CoTx. PreTx with 6 and 60 μM of DADS inhibited BaP-induced G2/M arrest by 68% and 78%, respectively. DADS, regardless of concentration or method, inhibited BaP-induced extracellular aqueous peroxide formation within 24 h. DADS attenuated BaP-induced DNA single-strand breaks at all time points through both DADS Pre- and CoTx, with significant inhibition for all treatments sustained after 6 h. DADS was effective in inhibiting BaP-induced cell proliferation, cell cycle transitions, reactive oxygen species, and DNA damage in a normal cell line, and thus may inhibit environmentally induced breast cancer initiation.

Background: General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation. Methods: A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane- induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. Results: In total, 112 rats (aged 7 days) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels. Conclusions: In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation. [ABSTRACT FROM AUTHOR]

Phencyclidine (PCP) is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist and exposing the developing brain to PCP has been shown to cause deficits in neurobehavioral functions. In the present study we tested the effects of PCP, as an NMDA receptor inhibitor, on the neuronal differentiation and biogenic amines levels including norepinephrine (NE), epinephrine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) in the rat pheochromocytoma (PC12) cells. After PC12 cells were differentiated with nerve growth factor (NGF) in the presence of PCP, NMDA binding kinetics, biogenic amines analysis and NMDA receptor protein expression assay were conducted. The results showed that NMDA receptor binding activities were significantly increased after differentiated with NGF in PC12 cells. B(max) values were increased in differentiated cells by four-folds, whereas K(d) values were not changed. All of biogenic amines were significantly increased in differentiated cells. On the other hand, PCP at 50 and 100 microM inhibited neuronal differentiation in a dose-dependent manner in NGF-stimulated PC12 cells without affecting cell viability. PCP treatment during differentiation significantly reduced NMDA binding activity and biogenic amine levels. Western blotting analysis revealed that NMDA receptor protein expression was significantly higher in NGF-differentiated cells and PCP treatment decreased the expression of NMDA receptor proteins. These results indicate that NMDA receptor functions and monoaminergic nervous systems are significantly stimulated during NGF-induced differentiation. PCP suppresses neuronal outgrowth and hampers neuronal functions possibly by inhibiting NMDA receptor functions and biogenic amine production, implying the suppressive effects of PCP exposure on neuronal developments.

Although the etiology of Parkinson's disease (PD) is not fully understood, there are numerous studies that have linked the increased risk for developing PD to pesticides exposure including paraquat (PQ). Moreover, the exposure to a combination of compounds or chemical mixtures has been suggested to further increase this risk. In the current study, the effects of PQ on the nigrostriatal dopaminergic system in male C57BL6 mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were examined to assess the impact of toxic substance mixtures exposure on neurochemical and behavioral changes. In this study, a low non-toxic dose of MPTP (10mg/kg) was injected once a day for 5 days and was followed by PQ (7 mg/kg) once a day for 6 days (subacute protocol) or once a week for 10 weeks (chronic protocol). The results from the subacute protocol showed that PQ reduced the turnover of dopamine (DA) as indicated by a 21% and a 22.3% decrease in dihydroxyphenyl acetic acid (DOPAC), homovanillic acid and increased S-adenosyl methionine/S-adenosyl homocysteine index (SAM/SAH) by 100%. However, the administration of PQ to MPTP primed mice resulted in the decrease of DOPAC, HVA, DA, by 35.8%, 35.2% and 22.1%, respectively. In addition, PQ decreased the total number of movements (TM) by 28% but MPTP plus PQ decreased TM by 41%. The SAM/SAH index showed that MPTP increased methylation by 33.3%, but MPTP plus PQ increased methylation by 81%. In the chronic protocol, the data showed that MPTP administration did not affect DA, DOPAC, and HVA levels. The administration of PQ led to significant decrease in DOPAC, HVA, and TD by 31.6%, 19.9%, and 21.2% respectively with no effect on DA levels. The MPTP plus PQ group showed reduced DA, DOPAC, HVA, and total distance traveled by 58.4%, 82.8%, 55.8%, and 83.9%, respectively. Meanwhile, PQ administration caused a reduction in tyrosine hydroxylase immunoreactivity in the substantia nigra, and this effect was more pronounced in MPTP pretreated mice. It was concluded from this study that prior treatment with MPTP potentiated the effects of PQ in reducing DA, DOPAC, HVA, TH immunoreactivity, locomotor activity, and increasing the methylation index. The enhanced effects of PQ following MPTP administration further support the role of toxic substance mixtures in causing Parkinson's disease.

In case of injury or disease, microglia are recruited to the site of the pathology and become activated as evidenced by morphological changes and expression of pro-inflammatory cytokines. Evidence suggests that microglia proliferate by cell division to create gliosis at the site of pathological conditions such as the amyloid plaques in Alzheimer's disease and the substantia nigra of Parkinson's disease patients. The hyperactivation of microglia contributes to neurotoxicity. In the present study we tested the hypothesis that anti-inflammatory compounds modulate the progression of cell cycle and induce apoptosis of the activated cells. We investigated the effects of ibuprofen (non-steroidal anti-inflammatory drug) and apigenin (a flavonoid with anti-inflammatory and anti-proliferative properties) on the cell cycle of the murine microglial cell line BV-2. The findings indicate that apigenin-induced cell cycle arrest preferentially in the G2/M phase and ibuprofen caused S phase arrest. The binding of annexin V-FITC to the membranes of cells which indicates the apoptotic process were examined, whereas the DNA was stained with propidium iodide. Both apigenin and ibuprofen induced apoptosis significantly in early and late stages. The induction of apoptosis by ibuprofen and apigenin was confirmed using TUNEL assay, revealing that 25 microM apigenin and 250 microM ibuprofen significantly increased apoptosis in BV-2 cells. The results from the present study suggest that anti-inflammatory compounds might inhibit microglial proliferation by modulating the cell cycle progression and apoptosis.

In many cases, development of insulin resistance has been linked to obesity and may contribute to mechanism of aging. The role of diet, irrespective of degree of obesity, in modulating insulin resistance and development of age degeneration disease remains uncertain. Lowered blood glucose levels are commonly associated with diet restriction (DR), which is an intervention shown to successfully retard aging and age associated disease. The effects of DR on blood glucose and insulin resistance were measured in yellow obese (A(vy)/A), lean black (a/a) mice and in another common inbred strain (B6C3F1) (at three different ages). The yellow obese mice become diabetic as a result of an insulin receptor defect which is not clearly understood. Insulin responses and radioinsulin binding were assayed in yellow obese and lean black mice fed either ad libitum (AL) or DR diets (YAL, BAL, YDR and YAL, respectively) at four different circadian intervals. The B6C3F1 controls were fed either AL (CAL) or DR (CDR) and measures were made at six circadian stages and three different ages. Within 23 days, DR produced a significant loss in body weight and a time-dependent 22-55% reduction in basal blood glucose levels in the yellow obese mice. Additionally, exogenous insulin produced circadian stage dependent (at the time of food intake) reductions in blood glucose in the YDR animals that were not present in YAL animals. (125)I-Insulin binding in liver was increased nearly 2-fold in YDR and BDR mice during the time of day that animals were active and eating. (125)I-Insulin binding was two-fold-higher in CDR mice at 4, 12 and >24 months of age. Binding decreased as a function of age in both the CAL and CDR animals. However, even in the >24 month group the CDR animals were found to have levels of binding that were as high as those found in younger CAL liver. The mechanism of action appears to be through resolution of insulin resistance by modulating an insulin receptor defect.

We examined the influences of dietary restriction (DR) on the circadian profile of liver catalase (CAT), glutathione peroxidase (GPx), and interacting systems required for removal of H2O2 (support systems), in 18-week old female Fischer 344 rats fed 60% of their ad libitum (AL) diet for six weeks. Food was presented to the DR animals during the early light-span. Regardless of diet, enzyme levels were generally consistent with circadian patterns. In CR animals, maximum activities often occurred at the time of food presentation. CAT and GPx activities generally were significantly higher in DR animals than in AL animals at the time of feeding. When assessing glucose-6-phosphate dehydrogenase (G6PDH) activity using saturating substrate (NADP(+)) concentrations, higher activities were seen at all times of day in the AL animals; however, when activity was measured in the presence of lower (i.e., physiologic) NADP(+) concentrations, the reverse was true. In contrast, glutathione reductase (GR) activity was not influenced by DR. Cytosolic levels of NADPH peaked and were higher in DR than in AL rodents prior to feeding. NADH levels were not influenced by diet, but did manifest a significant circadian pattern with a maximum occurring toward the middle of the dark span. These data suggest that even at a young age and following only a relatively brief duration of DR, there exists an enhanced enzymatic capability in rats subjected to DR to remove free radicals generated as a consequence of normal oxidative metabolism. Further, these data support emerging trends suggesting metabolic regulation of antioxidant defense systems in response to free radical generation.

Novel steroidal antiinflammatory antedrugs, 11 beta,20-dihydroxy-3,20-dioxo-3'-(ethoxycarbonyl)-isoxazolino[16,17 - d]pregna-1,4-diene (2a) and 9-fluoro-11 beta,20-dihydroxy-3,20-dioxo-3'-ethoxy- carbonylisoxazolino[16,17-d]pregna-1,4-diene (2b) were prepared in 97% yield via 1,3-dipolar cycloaddition of carbethoxyformonitrile (CEFNO) to 11 beta,21-dihydroxy-3,20-dioxopregna-1,4,-16-triene (1a) and 11 beta,21-dihydroxy-3,20-dioxo-9-fluoropregna-1,4,16-triene (1b), respectively, which were prepared via five steps from prednisolone and 9-fluoroprednisolone, respectively. The treatment of steroids 2a and 2b with acetic anhydride in pyridine led to the corresponding 21-acetates 3a and 3b, respectively, in 95% yield. Dose-response profiles of the croton oil-induced ear edema bioassay in rats were used to calculate the following ID50 values (nmol/ear resulting in a 50% reduction of edema): prednisolone (P), 540 nmol; 2b, 135 nmol; and 3b, 101 nmol. Inhibition of edema did not exceed 50% following application of either 2a or 3a. Relative potency calculations indicated that 2b was 4-fold and 3b 5.3-fold more potent than the parent compound P when applied topically. No significant adverse systemic effects were seen following treatments with 3b. These results suggest that C-9-fluorination, side-chain hydroxy group esterification, and [16 alpha,17 alpha-d]-3'-carbethoxyisoxazoline additions to the conventional steroid P improve topical antiinflammatory activity without concomitant increases in adverse systemic activity.

Cancer progression is primarily driven by the uncontrolled activation of cellular signaling pathways, with the PI3K/Akt/mTOR (PAMT) pathway playing a central role. This pathway significantly contributes to the proliferation and survival of cancer cells, and its hyperactivity is a major challenge in managing several types of malignancies. This article delves into the promising potential of carotenoids, natural pigments found in abundance in fruits and vegetables, as a novel therapeutic strategy for cancer treatment. By specifically targeting and inhibiting the PAMT pathway, carotenoids may effectively disrupt the growth and survival of cancer cells. The article examines the complex mechanisms underlying these interactions and highlights the obstacles faced in cancer treatment. It proposes a compelling approach to developing therapies that leverage natural products to target this critical pathway, offering a fresh perspective on cancer treatment. Further research is essential to enhance the therapeutic efficacy of these compounds., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Ethical approval Not applicable. Consent to Participate Not applicable. Consent for Publication Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer is one of the deadliest and most heterogeneous diseases. Cancers often develop drug resistance, which can lead to treatment failure or recurrence. Accordingly, anticancer compounds are essential for chemotherapy-resistant cancer cells. Phenolic compounds are of interest in the development of cancer drugs due to their medicinal properties and ability to target different molecular pathways. Gallic acid (GA), as one of the main components of phenol, which is abundantly present in plant compounds such as walnut, sumac, grapes, tea leaves, oak bark, and other plant compounds, has antitumor properties. GA can prevent cancer progression, cell invasion, and metastasis by targeting molecular pathways and is an effective complement to chemotherapy drugs and combating multidrug resistance (MDR). In this review, we discuss various mechanisms related to cancer, the therapeutic potential of GA, the antitumor properties of GA in various cancers, and the targeted delivery of GA with nanocarriers. [ABSTRACT FROM AUTHOR]

Male Sprague-Dawley rats weighing approximately 225 g and maintained under controlled lighting and temperature conditions, were used in this experiment. Animals were given morphine (10 mg/kg, i.p.) either at 10:00 hr or at 22:00 hr. One hour later, treated animals with their proper control were sacrificed and the mucosa of the stomach, duodenum, ileum and colon were separated and assayed for acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities. Data obtained indicate that morphine administration during the light phase resulted in a significant increase (p less than 0.01) in AChE activity in the colon, with no significant effect on the stomach, duodenum or the ileum. There was also significant increase (p less than 0.05) in ChAT activity in the stomach and the duodenum as a result of morphine administration during the light phase, with no effect on other tissues studied. During the dark phase, there were no significant changes observed in AChE activity of all tissues examined following morphine administration. However, the determination of ChAT activity during the dark phase, following morphine treatment, showed a significant increase (p less than 0.01) in the duodenum and the ileum, with a significant decline (P less than 0.05) in the colon. Results obtained from this study indicate that gastrointestinal changes seen after morphine administration could be due to changes in the activity of the cholinergic enzymes and these changes may be diurnally controlled.

Male Sprague-Dawley rats maintained under controlled lighting and temperature conditions were used in this experiment. Animals were exposed to acute cold (4 degrees C) and immobilization stress for one hour, exposed to cold stress for 7 days (chronic stress) or treated with corticosterone (2 mg/kg) 1 hr prior to sacrificing. Animals with their proper controls were sacrificed and the stomach, duodenum, ileum and colon were separated and assayed for choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities. The data obtained indicated that exposure to acute stress resulted in significant decline in ChAT activity in all tissues studied. The administration of corticosterone resulted in significant decline in ChAT activity in all tissues studied except for the duodenum. Meanwhile, the exposure to chronic stress did not have any significant effect on ChAT activity. On the other hand, acute stress caused significant increase in AChE activity in all tissues studied except for the ileum and stomach. The duodenal AChE activity of stressed animals increased thirty-fold when compared to control. The administration of glucocorticoids significantly reduced AChE in all tissues studied, except for the duodenum and stomach where there was thirty-two-fold increase as compared to the control levels. The exposure to chronic stress also caused significant increase in AChE of all tissues studied, except for the colon. The results of this experiments indicate that the duodenal AChE is extremely sensitive to stress or glucocorticoids and that stress induced changes in the cholinergic enzymes of the gastrointestinal tract may be mediated by adrenal steroids.

Male Sprague-Dawley rats weighing between 180 and 220 g and maintained under controlled lighting and temperature conditions were used in this experiment. Animals were given ethanol (3 g/kg, p.o.) 24 h after fasting. One group was given ethanol at 10.00 h (light phase) and the other at 22.00 h (dark phase). One hour later, the treated animals with their proper controls were sacrificed and the mucosa of the stomach, duodenum, ileum and colon were separated and assayed for choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities. Data obtained indicate that the administration of ethanol resulted in significant decline (p less than 0.01) in ChAT activity in the stomach and the colon during the light phase. A significant increase (p less than 0.01) in ChAT activity was also noted in the ileum during the dark phase. There was a significant decrease (p less than 0.01) in AChE activity in the stomach during the dark phase. The administration of ethanol also resulted in a significant decline in AChE activity (p less than 0.05) in the duodenum and the colon (p less than 0.01). The results obtained indicate that the gastrointestinal changes caused by ethanol administration may be related to changes in the cholinergic enzymes of the mucosa of the gastrointestinal tract.

Male Sprague-Dawley rats maintained under controlled environmental conditions were used. Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in the cerebral cortex, bulbus olfactorius, midbrain, hypothalamus, hippocampus, cerebellum, pons and medulla oblongata of control rats and rats treated with apomorphine (15 mg/kg, i.p.) after a single dose or after a second dose administered 24 h later at 10.00 or 22.00 h. Results of this experiment indicate that the repeated administration of apomorphine at 10.00 h was associated with rapid development of tolerance to the hypothermic action of this drug. A single injection of apomorphine resulted in significant (p less than 0.01) decrease of AChE and significant increase of ChAT activity (p less than 0.01) in the cortex, hypothalamus and pons. There were no significant differences between tolerant and control animals in the activities of AChE or ChAT in the bulbus olfactorius, cerebral cortex, midbrain, pons or medulla. On the other hand, repeated administration of apomorphine at 22.00 h was not associated with tolerance to the hypothermic action of this drug. A single injection of apomorphine at 22.00 h resulted in significant (p less than 0.01) increase in AChE activity of the midbrain, hippocampus, and the medulla oblongata with no significant changes in the cerebral cortex and bulbus olfactorius. There was a significant decline (p less than 0.01) of ChAT activity of the hypothalamus, hippocampus, cerebral cortex and the medulla oblongata (p less than 0.05). Meanwhile, there was a significant (p less than 0.05) increase of ChAT activity of the midbrain with no significant changes in the cerebellum, pons and the bulbus olfactorius.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study, male Sprague-Dawley rats maintained under controlled environmental conditions were used. Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in cerebral cortex, bulbus olfactorius, midbrain, hypothalamus, hippocampus, cerebellum, pons and medulla oblongata in control rats and rats treated with morphine (10 mg/kg) for 1 or 2 days. Repeated administration of morphine was associated with a decline in the degree of analgesia produced. Significant increase (p less than 0.01) in AChE activity of the medulla oblongata was observed following morphine administration for 1 or 2 days. A single injection of morphine resulted in a significant decline (p less than 0.01) in ChAT activity of hypothalamus, cerebellum and medulla oblongata. However, no such decline could be observed after 2 consecutive daily injections of morphine. In the cerebral cortex there was a significant decline (p less than 0.01) in ChAT activity after the second administration of morphine. These findings indicate that the changes in the responsiveness of the brain cholinergic enzymes following repeated morphine administration may in part explain the rapid development of tolerance to the analgesic effect of morphine.

Background: Apigenin has been reported to exhibit anti-inflammatory and anti-oxidative activities. This study aimed to investigate the protective role of Apigenin on chemotherapy-induced peripheral neuropathy (CIPN). Methods: CIPN mouse model was established using Paclitaxel treatment. Hot plate and tail prick latency tests were performed to examine the allodynia and hyperalgesia behaviors. Antiinflammatory and anti-oxidative effects of Apigenin on CIPN were determined by enzyme-linked immunosorbent (ELISA) assay, Western blot, and qRT-PCR. Nuclear recruitment of nuclear factor erythroid 2-related factor 2 (NRF2) was analyzed to evaluate the underlying mechanisms of the protective effects of Apigenin. Results: Apigenin significantly alleviated CIPN-induced nociceptive behaviors of CIPN mice. It also decreased the TNF-α and IL-1β levels, suppressed oxidative stress and inflammation in the surgical spinal cord tissues. Mechanistically, Apigenin altered the pro-inflammatory and anti-inflammatory phenotypes ratio of microglia through promoting the nuclear recruitment of NRF2 and activating the NRF2/Antioxidant Response Element (ARE) signaling pathway. Conclusions: In summary, Apigenin relieves CIPN by regulating microglia activation and polarization, which provides a potential therapeutic strategy for CIPN treatment. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer which is characterized by the absence of progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2, thus, TNBC patient tumour does not respond to the endocrine therapy. TNBC is highly invasive, highly metastatic, and shows poor prognosis, recurrence, and short survival rate. Surgery, chemotherapy, and radiotherapy are now used as treatments. Despite the wide range of treatment choices, the main drawbacks of current therapies include drug resistance, decreased effectiveness, recurrence within 5 years, and a variety of side-effects. A unique targeted approach is therefore desperately required for the treatment of TNBC. Researchers now have fresh perspectives on the tailored strategy for treating TNBC thanks to phytochemicals. Phytochemicals have shown antiproliferative properties in TNBC and also overcome the drawbacks like recurrence, toxicity, adverse effect, and quality of life. This review highlights different phytochemicals and their potential to target signalling pathways and gene expression to induce apoptosis, cell cycle arrest, inhibition of metastasis, and angiogenesis. [ABSTRACT FROM AUTHOR]

Immunotherapy is a type of treatment that uses our own immune system to fight cancer. Studies have shown that traditional Chinese medicine (TCM) has antitumor activity and can enhance host immunity. This article briefly describes the immunomodulatory and escape mechanisms in tumors, as well as highlights and summarizes the antitumor immunomodulatory activities of some representative active ingredients of TCM. Finally, this article puts forward some opinions on the future research and clinical application of TCM, aiming to promote the clinical applications of TCM in tumor immunotherapy and to provide new ideas for the research of tumor immunotherapy using TCM. [ABSTRACT FROM AUTHOR]

In the post-genomic era, the data provided by complete genome sequencing could not answer several fundamental questions about the causes of many noninfectious diseases, diagnostic biomarkers, and novel therapeutic approaches. The rapidly expanding understanding of epigenetic mechanisms, as well as widespread acceptance of their hypothesized role in disease induction, facilitated the development of a number of novel diagnostic markers and therapeutic concepts. Epigenetic aberrations are reversible in nature, which enables the treatment of serious incurable diseases. Therefore, the interest in epigenetic modulatory effects has increased over the last decade, so about 60,000 publications discussing the expression of epigenetics could be detected in the PubMed database. Out of these, 58,442 were published alone in the last 10 years, including 17,672 reviews (69 historical articles), 314 clinical trials, 202 case reports, 197 meta-analyses, 156 letters to the editor, 108 randomized controlled trials, 87 observation studies, 40 book chapters, 22 published lectures, and 2 clinical trial protocols. The remaining publications are either miscellaneous or a mixture of the previously mentioned items. According to the species and gender, the publications included 44,589 human studies (17,106 females, 14,509 males, and the gender is not mentioned in the remaining papers) and 30,253 animal studies. In the present work, the role of epigenetic modulations in health and disease and the influencing factors in epigenetics are discussed. [ABSTRACT FROM AUTHOR]

Isoxazole and its derivatives derived from natural resources are very few. However, they have several applications in pharmaceutical industries, including antimicrobial, antitumor, anticancer, antifungal, and antibacterial activities. As a result, this research aimed to design a novel one-pot green approach to synthesize new oxazole derivatives. The derivatives were further explored for their antibacterial and antioxidant activities together with their density functional theory (DFT) analysis. Characterization of newly synthesized moieties was done by IR, 1H NMR, 13C NMR, CHN analysis, & single-crystal X-ray Crystallography. Further, these compounds were examined for their antibacterial potential by using Gentamycin as a standard drug against S. aureus and E. coli bacterial strains. The derivatives 4a, 4c, 4d, 4f, 4j, and 4k possessed excellent antibacterial potential against former, while 4c and 5 showed the highest activity against the later one. The derivatives were also analyzed for their antioxidant activities by using free radical scavenging (ABTS. & DPPH assays), and total antioxidant capacity. Here also, 4a, 4d, 4e, 4k, 4l, 4m, and 5 exhibited the most promising results. Finally, the DFT analysis was achieved by using the B3LYP methodology with a 6–311 + G(d,p) basis set to study the electronic structure of molecules and analysis of chemical reactivity descriptors such as hardness (η), Mulliken electronegativity (χ), chemical potential (μ) and electrophilicity (ω). These properties were calculated from the levels of the predicted frontier molecular orbitals and their energy gap. [ABSTRACT FROM AUTHOR]

Background: Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD). Methods: We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression. Results: Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening. Conclusions: In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution. [ABSTRACT FROM AUTHOR]

The incidence of cancer has been growing worldwide. Better survival rates following the administration of novel drugs and new combination therapies may concomitantly cause concern regarding the long‐term adverse effects of cancer therapy, for example, second primary malignancies. Moreover, overcoming tumour resistance to anticancer agents has been long considered as a critical challenge in cancer research. Some low toxic adjuvants such as herb‐derived molecules may be of interest for chemoprevention and overcoming the resistance of malignancies to cancer therapy. Apigenin is a plant‐derived molecule with attractive properties for chemoprevention, for instance, promising anti‐tumour effects, which may make it a desirable adjuvant to reduce genomic instability and the risks of second malignancies among normal tissues. Moreover, it may improve the efficiency of anticancer modalities. This paper aims to review various effects of apigenin in both normal tissues and malignancies. In addition, we explain how apigenin may have the ability to protect usual cells against the genotoxic repercussions following radiotherapy and chemotherapy. Furthermore, the inhibitory effects of apigenin on tumours will be discussed. [ABSTRACT FROM AUTHOR]

Cancer is an illness characterized by abnormal cell development and the capability to infiltrate or spread to rest of the body. A tumor is the term for this abnormal growth that develops in solid tissues like an organ, muscle, or bone and can spread to other parts of the body through the blood and lymphatic systems. Nutrition is a critical and immortal environmental component in the development of all living organisms encoding the relationship between a person's nutrition and their genes. Nutrients have the ability to modify gene expression and persuade alterations in DNA and protein molecules which is researched scientifically in nutrigenomics. These interactions have a significant impact on the pharmacokinetic properties of bioactive dietary components as well as their site of action/molecular targets. Nutrigenomics encompasses nutrigenetics, epigenetics, and transcriptomics as well as other "omic" disciplines like proteomics and metabolomics to explain the vast disparities in cancer risk among people with roughly similar life style. Clinical trials and researches have evidenced that alternation of dietary habits is potentially one of the key approaches for reducing cancer risk in an individual. In this article, we will target how nutrigenomics and functional food work as preventive therapy in reducing the risk of cancer. [ABSTRACT FROM AUTHOR]

Argemone mexicana(Pepaveraceae) is an important medicinal plant commonly known as 'maxican prickly poppy' and is traditionally used to treat skin diseases. In the present study, the extract/fractions of aerial parts of A. mexicana after carrying out the organoleptic characteristics were sequentially extracted with the solvents of increasing polarities. Total fractions were examined for their radical scavenging activities in DPPH and DNA nicking assays. Among all, maximum antioxidant activity was shown by chloroform fraction (AmC) in DPPH assay with IC50 of 26.12 μg/ml, and DNA nicking assay showed 80.91% protective potential. The AmC fraction was analyzed for its antibacterial, cytotoxic potential, cell cycle analysis, mitochondrial membrane potential (MMP) and accumulation of reactive oxygen species (ROS) using A431 cell line. The AmC fraction exhibited remarkable antibacterial activity against bacterial strains in the order Klebsiella pneumoniae> Bacillussubtilis> Salmonella typhi> Staphylococcus epidermidis. The cytotoxic potential of the AmC fraction was analyzed in skin epidermoid carcinoma (A431) cells, osteosarcoma (MG-63) and cervical (HeLa) cell lines with a GI50 value of 47.04 μg/ml, 91.46 μg/ml and 102.90 μg/ml, respectively. The AmC fraction was extended further to explore its role in cell death using A431 cell line. Phase contrast and scanning electron microscopic studies on A431 cells exhibited all the characteristics indicative of apoptosis, viz., viability loss, cell shrinkage, cell rounding-off, DNA fragmentation and formation of apoptotic bodies. Flow cytometric analysis revealed enhanced ROS level, decreased MMP and arrest cell cycle at the G0/G1 phase further strengthened cell death by apoptosis. Increased expressions of apoptotic markers (p53, PUMA, cyt c, Fas and Apaf-1) were confirmed by RT-qPCR analysis. Furthermore, the AmC fraction was subjected to ultra-high-performance liquid chromatography, which revealed the presence of different polyphenols in the order: caffeic acid> epicatechin> kaempferol> chlorogenic acid> gallic acid> catechin> ellagic acid >umbeliferone> quercetin> coumaric acid. A critical analysis of results revealed that the AmC fraction induced cell death in epidermoid carcinoma cells via ROS and p53-mediated apoptotic pathway which may be ascribed to the presence of polyphenols in it. [ABSTRACT FROM AUTHOR]

Simple and efficient method was established for the synthesis of a new family of 14α-O-(andrographolide-3-subsitutedisoxazole-5-carboxylate) derivatives (10a-j) from naturally occurring andrographolide (1) by selective esterification with propiolic acid at C-14 using protection and deprotection strategy followed by metal free 1,3-dipolar cycloaddition with aryl nitrile oxides. All the synthesised derivatives were tested for their cytotoxicity against HCT-15, HeLa and DU145 cell lines. Most of the compounds exhibited improved cytotoxic activity compared to the parent molecule andrographolide (1), as the compounds 10b, 10c, 10i, 10j, 11d and 11f showed significant cytotoxicity against three cancer cell lines. Except the compound 10b and 11d, all the compounds did not inhibit the normal cell line (VERO). Based on these studies isoxazole ester derivatives at C-14 of andrographolide with various substitutions promoting anticancer activities and better safety profiles. Further studies in this direction with improved water solubility and oral bioavailability are in progress in future. [ABSTRACT FROM AUTHOR]

One of the uses of fossil fuels which are finite and non-renewable is for firing non-ferrous melting furnace in our metal industries. Early exhaustion coupled with their environmental pollution associated with their burning, necessitated the search for alternatives. So agricultural waste briquette such as palm kernel shell briquette was considered in this study. Lead, zinc, aluminum, brass and bronze were selected for melting. The briquettes were used to fire nonferrous melting furnace to melt lead, zinc, aluminum. Brass and bonze. Combustion, melting and flue gas temperatures were measured and their variations with time were shown. The results showed that, lead zinc and aluminum melted and reached their pouring temperatures of 425°C in 55 minutes, 526°C in 55 minutes and 736°C in 80 minutes respectively. Brass and bronze could only be heated to maximum temperatures of 883°C in 85 minutes and 826°C in 85 minutes respectively. It can be concluded that agricultural waste briquettes are good alternative renewable energy sources for firing crucible furnace for low temperature melting metals. [ABSTRACT FROM AUTHOR]

The time and energy expended in shelling corn manually have necessitated the detailed design and construction of a modern electric corn shelling machine. The major problems associated with the manual corn shelling machine were the high level of fatigue of the operator and low shelling capacity, leading to reduced productivity. These problems motivated the construction of a sheller with a simple design, that employs a swift mechanism and pulley drive, is simple to use and maintain and results in improved efficiency. Results obtained show that the electric corn shelling machine developed in this study is cost effective and has a shelling efficiency of 91.4%, whereas the manual corn sheller was shown to have an efficiency of 45% or less. Therefore, if the electric corn shelling machine were used, especially in rural settings, it could optimize the time and energy currently taken to shell corn manually on a large scale. [ABSTRACT FROM AUTHOR]

Cassava grating is a size reduction process that converts peeled cassava tubers into cassava mash. Grating cassava tubers using the conventional graters makes the process tedious and labor‐intensive. Thus, a double‐action cassava grating machine with an automated contact plate was developed, and the machine performance was evaluated. A 3 × 5 central composite rotatable design (CCRD) of response surface methodology (RSM) was adopted for the performance test experiments. The machine parameters are grating speeds, gs (765, 865, and 965 rpm), conveying time, ct (7.37, 5.84, 4.40, 3.00, and 1.69 s); (6.67, 5.00, 3.55, 2.40, and 1.19 s); and (5.97, 4.38, 3.19, 2.00, and 0.97 s) at 765, 865, and 965 rpm respectively; and the contact plate control timing, cpct (5.85, 11.91, 17.16, 26.69, and 30.44 s) were selected. The throughput (TP) and grating efficiency (GE) were determined. Data analysis was carried out using multiple linear regressions at α = 0.05. Maximum TP of 26.64 kg/hr was obtained at gs (965 rpm), ct (3.19 s), and tscp (5.85 s), while maximum GE of 74.25% was obtained at gs (765 rpm), ct (4.40 s), and tscp (17.16 s). TP increased with an increase in gs, but decreased with an increase in cpct and ct. Hence, the developed cassava grating machine is a viable option to large scale cassava processors due to the ease of operation, less processing time, and less man‐power demand as a result of machine automation. Practical Applications: Despite a considerable improvement in the advancement of machines for grating cassava tubers, there is still some tedious activities experienced during the process of cassava grating. To this end, there is a need for innovation of technological application in cassava grating. Thus, a double‐action cassava grater with automated contact plate capable of integrating several operations involved in cassava grating and finishing in one pass was developed, and the performance was evaluated. CCRD of RSM was employed to design the experiment to evaluate the effects of the machine operating parameters on the performance of the cassava grating system based on the machine throughput and grating efficiency. The developed cassava grating system will be a useful option for large‐scale cassava processing due to the continuous grating operation achieve in the machine, which is suitable for cassava processing industry where the large scale of cassava tubers is being processed. [ABSTRACT FROM AUTHOR]

The neurotoxin 1-methyl,4-phenyl-1,2,3,6-tetrahydropiridine (MPTP) is widely used to produce experimental parkinsonism in rodents and primates. Among different administration protocols, continuous or chronic exposure to small amounts of MPTP is reported to better mimic cell pathology reminiscent of Parkinson's disease (PD). Catecholamine neurons are the most sensitive to MPTP neurotoxicity; however, recent studies have found that MPTP alters the fine anatomy of the spinal cord including motor neurons, thus overlapping again with the spinal cord involvement documented in PD. In the present study, we demonstrate that chronic exposure to low amounts of MPTP (10 mg/kg daily, × 21 days) significantly reduces motor neurons in the ventral lumbar spinal cord while increasing α-synuclein immune-staining within the ventral horn. Spinal cord involvement in MPTP-treated mice extends to Calbindin D28 KDa immune-reactive neurons other than motor neurons within lamina VII. These results were obtained in the absence of significant reduction of dopaminergic cell bodies in the Substantia Nigra pars compacta, while a slight decrease was documented in striatal tyrosine hydroxylase immune-staining. Thus, the present study highlights neuropathological similarities between dopaminergic neurons and spinal motor neurons and supports the pathological involvement of spinal cord in PD and experimental MPTP-induced parkinsonism. Remarkably, the toxic threshold for motor neurons appears to be lower compared with nigral dopaminergic neurons following a chronic pattern of MPTP intoxication. This sharply contrasts with previous studies showing that MPTP intoxication produces comparable neuronal loss within spinal cord and Substantia Nigra. [ABSTRACT FROM AUTHOR]

Neuroinflammation and microglial activation are two important hallmarks of neurodegenerative diseases. Continuous microglial activation may cause the release of several cytotoxic molecules, including many cytokines that are involved in the inflammatory process. Therefore, attenuating inflammation caused by activated microglia may be an approach for the therapeutic management of neurodegenerative diseases. In addition, many studies have reported that polyphenol pentagalloyl glucose (1,2,3,4,6-penta-O-galloyl-β-D-glucose; PGG) is a molecule with potent anti-inflammatory effects, such as inhibiting the release of proinflammatory cytokines. Our previous studies revealed that PGG attenuated the expression of two inflammatory cytokines (murine monocyte chemoattractant protein-5 and pro-metalloproteinase-9) in lipopolysaccharide/interferon γ-activated BV-٢ microglial cells. Additionally, PGG modulated the NF-κB and MAPK signaling pathways by altering genes and proteins, which may affect the MAPK cascade and NF-κB activation. The aim of the present study was to investigate the ability of PGG to modulate the expression of proteins released in activated BV-2 microglial cells, which may be involved in the pathological process of inflammation and neurodegeneration. Proteomic analysis of activated BV-2 cells identified 17 proteins whose expression levels were significantly downregulated by PGG, including septin-7, ataxin-2, and adenylosuccinate synthetase isozyme 2 (ADSS). These proteins were previously described as being highly expressed in neurodegenerative diseases and/or involved in the signaling pathways associated with the formation and growth of neuronal connections and the control of Alzheimer's disease pathogenesis. The inhibitory effect of PGG on ataxin-2, septin-7 and ADSS was further confirmed at the protein and transcriptional levels. Therefore, the obtained results suggest that PGG, with its potent inhibitory effects on ataxin-2, septin-7 and ADSS, may have potential use in the therapeutic management of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Phytochemicals are ubiquitous in naturally occurring dietary elements that exhibits diverse pharmacological properties over various pathological disorders, including cancer. Voltage gated K+ (KV) channel in the plasma membrane contributes to wide range of cellular processes including cancer progression. Therefore, modulation of KV channel is being considered as a novel potential target for cancer therapy. The whole cell patch clamp technique was used to record the modulatory effect of chrysin, naringenin, caffeic acid, gallic acid, and zingerone on delayed rectifier potassium current (IK) in human prostate cancer cells LNCaP and PC-3. Among the tested compounds, zingerone blocked IK in a concentration-dependent manner in LNCaP cells and estimated the IC50 value of 141 μM and Emax was 81.3%. Further analysis of KV channel activation kinetics showed that zingerone induces a positive shift in the activation curve in LNCaP cells, whereas the inhibitory effect of gallic acid on IK was significantly less potent than the inhibition caused by zingerone. However, chrysin, naringenin, and caffeic acid did not modulate the KV channel conductance in LNCaP or PC-3 cells. Our findings confirmed that not all the tested phytochemicals to be effective modulators of IK and suggested that IK inhibitory effect of zingerone and gallic acid may be responsible for their anticancer effects in prostate cancer cells. [ABSTRACT FROM AUTHOR]

Recently, certain polybrominated diphenyl ethers (PBDEs) have been listed as persistent organic pollutants (POPs) in the Stockholm Convention. In this study, a preliminary material and substance flow analysis of commercial pentabromodiphenyl ether (c-PentaBDE) was conducted for motor vehicles—a major use sector for POP-PBDE in polyurethane (PUR) foam—for Nigeria. The methodology of the Stockholm Convention PBDE inventory guidance was used for the calculation of c-PentaBDE. Material/substance flow analysis was conducted applying the STAN software. The time frame for this analysis was 1980-2010, considering that this was the period when POP-PBDE-containing vehicles were largely imported into Nigeria.It is estimated that the approximately 19 million passenger cars imported from 1980 to 2010 contained ca. 270 t of POP-PBDEs in ca. 401,000 t of PUR foam. A major share of cars from the USA and only a small share of cars from Europe and Asia were impacted. This simplified material and substance flow of PUR foams and POP-PBDEs in motor vehicles demonstrated the potential for environmental/human contamination and pollution of recycling/reuse for Nigeria and other developing countries.The study developed the first preliminary inventory of end-of-life vehicles for Nigeria, following which the environment ministry has taken up the important issue of end-of-life vehicles management. Considering that a range of other pollutants are contained in vehicles (e.g. heavy metals, flame retardants, PCBs, chlorofluorocarbons, hydrofluorocarbons and waste oil), this initiated activity should finally lead to an integrated management of pollutants and resources from the transport sector. [ABSTRACT FROM AUTHOR]

Background and Aim: Phenolic compounds form an important category of antioxidants that have important biological activities, such as anticancer, antifungal, antibacterial and antiviral effects. In this study, the anticancer effects of Gallic acid and P-Coumaric acid were studied on MDA-MB-231 human breast cancer cell line. Materials and Methods: In this experimental study, human breast cancer cells of MDA-MB-231 (104 cells) were treated with Gallic acid, P-Coumaric Acid in different concentrations (0, 10, 25, 50 and 100 ?g / ml) for 24 hours. The cell viability of treated cells was determined using MTT assay and invert light microscopy. Results: The cell viability of treated cell with 100 ?g/ml Gallic cell is about 16%, and in the case of paracoumaric acid at the similar concentration, the cell viability is about 83%. The morphological study confirmed the results of MTT using an inverted light microscope. Conclusion: The inhibitory effect of Gallic acid in MDA-MB-231 human breast cancer cells is higher in comparison to P-Coumaric acid at the similar concentration. According to the study, this effect could be due to the difference in the number of hydroxyl groups on these compounds. [ABSTRACT FROM AUTHOR]

For comprehensive studies on drugs primarily in the form of biomimetic systems, electronic parameters are becoming essential tools in elucidating the structures of the investigated compounds. In this study we present the synthesis, characterization, and evaluation of biological potency of 4(a-g), 5(a-g), and 7(a-g) by conducting structure-activity relationship (SAR) studies. Further conducting density functional theory (DFT) simulation studies for entitled compounds 4(a-g), 5(a-g), and 7(a-g) allowed us to fully study the effect of the changes of electronic and molecular structures on their biological activity by demonstrating the role of frontier molecular orbitals, in particular LUMO. The electron withdrawing nitro group substituted compounds 5d and 7d have higher activity than all other active compounds. Thus, the results strongly suggest that the SARs are in good agreement with simulation studies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered to manage the pain typically found in patients suffering from pancreatitis. NSAIDs also display anti-proliferative activity against cancer cells; however, their effects on normal, untransformed cells are poorly understood. Here, we evaluated whether NSAIDs inhibit the proliferation of pancreatic acinar cells during the development of acute pancreatitis.Experimental Approach: The NSAIDs ibuprofen and diclofenac were administered to C57BL/6 mice after induction of pancreatitis with serial injections of cerulein. In addition, ibuprofen was administered concomitantly with 3,5,3-L-tri-iodothyronine (T3), which induces acinar cell proliferation in the absence of tissue inflammation. The development of pancreatic inflammation, acinar de-differentiation into metaplastic lesions and acinar proliferation were quantified by histochemical, biochemical and RT-PCR approaches.Key Results: Therapeutic ibuprofen treatment selectively reduced pancreatic infiltration of activated macrophages in vivo, and M1 macrophage polarization and pro-inflammatory cytokine expression both in vivo and in vitro. Reduced macrophage activation was accompanied by reduced acinar de-differentiation into acinar-to-ductal metaplasia. Acinar proliferation was significantly impaired in the presence of ibuprofen and diclofenac, as demonstrated at both the level of proliferation markers and expression of cell cycle regulators. Ibuprofen also reduced acinar cell proliferation induced by mitogenic stimulation with T3, a treatment that does not elicit pancreatic inflammation.Conclusions and Implications: Our study provides evidence that the NSAIDs ibuprofen and diclofenac inhibit pancreatic acinar cell division. This suggests that prolonged treatment with these NSAIDs may negatively affect the regeneration of the pancreas and further studies are needed to confirm these findings in a clinical setting.Linked Articles: This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most commonly diagnosed and frequently occurred cancer in the males globally. The current treatment strategies available to treat prostate cancer are not much effective and express various adverse effects. Hence, there is an urgent need to identify novel treatment that can improve patient outcome. From times immemorial, natural products are highly recognized for novel drug development for various diseases including cancer. Cancer cells generally maintain higher basal levels of reactive oxygen species (ROS) when compared to normal cells due to its high metabolic rate. However, initiation of excess intracellular ROS production can not be tolerated by the cancer cells and induce several cell death signals which are in contrast to normal cells. Therefore, small molecules of natural origin that induce ROS can potentially kill cancer cells in specific and provide a better opportunity to develop a novel drug therapy. In this review, we elaborated various classes of medicinal compounds and their mechanism of killing prostate cancer cells through direct or indirect ROS generation. This can generate a novel thought to develop promising drug candidate to treat prostate cancer patients., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Paraquat (PQ) administration consists in a chemical model that mimics phenotypes observed in Parkinson's disease (PD), due to its ability to induce changes in dopaminergic system and oxidative stress. The aim of this study was to evaluate the actions of PQ in behavioral functions of adult zebrafish and its influence on oxidative stress biomarkers in brain samples. PQ (20 mg/kg) was administered intraperitoneally with six injections for 16 days (one injection every 3 days). PQ-treated group showed a significant decrease in the time spent in the bottom section and a shorter latency to enter the top area in the novel tank test. Moreover, PQ-exposed fish showed a significant decrease in the number and duration of risk assessment episodes in the light-dark test, as well as an increase in the agonistic behavior in the mirror-induced aggression (MIA) test. PQ induced brain damage by decreasing mitochondrial viability. Concerning the antioxidant defense system, PQ increased catalase (CAT) and glutathione peroxidase (GPx) activities, as well as the non-protein sulfhydryl content (NPSH), but did not change ROS formation and decreased lipid peroxidation. We demonstrate, for the first time, that PQ induces an increase in aggressive behavior, alters non-motor patterns associated to defensive behaviors, and changes redox parameters in zebrafish brain. Overall, our findings may serve as useful tools to investigate the interaction between behavioral and neurochemical impairments triggered by PQ administration in zebrafish. [ABSTRACT FROM AUTHOR]

This article follows the previously published study on the mechanical behaviour of oil palm kernels under compression loading. A slight change in deformation of the heat-treated kernels was observed at force 100 kN and speed 60 mm/min. Therefore, a greater force was required to produce higher percentage kernel oil. In this present study, however, both roasted and unroasted kernels were compressed in a vessel with diameter of 60 mmat varying forces from 150, 200, 250 and 300 kN and speed 10 mm/min aimed at determining the optimal pressing force without serration effect on the force-deformation curve. [ABSTRACT FROM AUTHOR]

Tannins, polyphenols in medicinal plants, have been divided into two groups of hydrolysable and condensed tannins, including gallotannins, ellagitannins, and (-)-epigallocatechin-3-gallate (EGCG). Potent anticancer activities have been observed in tannins (especially EGCG) with multiple mechanisms, such as apoptosis, cell cycle arrest, and inhibition of invasion and metastases. Furthermore, the combinational effects of tannins and anticancer drugs have been demonstrated in this review, including chemoprotective, chemosensitive, and antagonizing effects accompanying with anticancer effect. However, the applications of tannins have been hindered due to their poor liposolubility, low bioavailability, off-taste, and shorter half-life time in human body, such as EGCG, gallic acid, and ellagic acid. To tackle these obstacles, novel drug delivery systems have been employed to deliver tannins with the aim of improving their applications, such as gelatin nanoparticles, micelles, nanogold, liposomes, and so on. In this review, the chemical characteristics, anticancer properties, and drug delivery systems of tannins were discussed with an attempt to provide a systemic reference to promote the development of tannins as anticancer agents. [ABSTRACT FROM AUTHOR]

The study described the oil point and mechanical properties of roasted and unroasted bulk oil palm kernels under compression loading. The literature information available is very limited. A universal compression testing machine and vessel diameter of 60 mm with a plunger were used by applying maximum force of 100 kN and speed ranging from 5 to 25 mm min-1. The initial pressing height of the bulk kernels was measured at 40 mm. The oil point was determined by a litmus test for each deformation level of 5, 10, 15, 20, and 25 mm at a minimum speed of 5 mm min-1. The measured parameters were the deformation, deformation energy, oil yield, oil point strain and oil point pressure. Clearly, the roasted bulk kernels required less deformation energy compared to the unroasted kernels for recovering the kernel oil. However, both kernels were not permanently deformed. The average oil point strain was determined at 0.57. The study is an essential contribution to pursuing innovative methods for processing palm kernel oil in rural areas of developing countries. [ABSTRACT FROM AUTHOR]

Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators ( n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE ( n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter ( P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter ( P = 0.03) among applicators >59 years and reduced LINE-1 DNAm ( P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19-29, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) pathogenesis inevitably involves neuroinflammatory responses attained through contribution of both neuron and glial cells. Investigation done in both experimental models of PD and in samples of PD patients suggested the involvement of both central and peripheral inflammatory responses during PD pathogenesis. Such neuroinflammatory responses could be regulated by neuron-glia interaction which is one of the recently focused areas in the field of disease diagnosis, pathogenesis and therapeutics. Such aggravated neuroinflammatory responses during PD are very well associated with augmented levels of cyclooxygenase (COX). An increased expression of cyclooxygenase (COX) with a concomitant increase in the prostaglandin E2 (PGE2) levels has been observed during PD pathology. Ibuprofen is one of the non-steroidal anti-inflammatory drugs (NSAID) and clinically being used for PD patients. This review focuses on the neuroinflammatory responses during PD pathology as well as the effect of ibuprofen on various disease related signaling factors and mechanisms involving nitrosative stress, neurotransmission, neuronal communication and peroxisome proliferator-activated receptor-γ. Such mechanistic effect of ibuprofen has been mostly reported in experimental models of PD and clinical investigations are still required. Since oxidative neuronal death is one of the major neurodegenerative mechanisms in PD, the antioxidant capacity of ibuprofen along with its antidepressant effects have also been discussed. This review will direct the readers towards fulfilling the existing gaps in the mechanistic aspect of ibuprofen and enhance its clinical relevance in PD therapeutics and probably in other age-related neurodegenerative diseases.