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This investigation was performed to analyze the biological efficiency of metabolites extracted from actinobacterium, SRV02 strain. The doses of MIC and MBC signifies the control of bacterial strains and maximum inhibition. The presence of chemical metabolite-rich ethyl acetate extracts was responsible for the bactericidal effects. Furthermore, the cytotoxic capability of an ethyl acetate extract rich in metabolites was evaluated using non-small cell lung cancer cell lines. The changes in cell morphology were confirmed through different AO/EB, Hoechst and DCFH-DA fluorescent staining. Fourier transform infrared spectroscopy (FT-IR) and Gas Chromatography Mass Spectrometry (GC-MS) analysis were used to confirm the presence of chemical components in the crude ethyl acetate extract. The FT-IR analysis revealed the presence of alkanes (C-H stretch), primary amines (with C = C stretch), alkanes (C = C stretch), aliphatic amines (C –N stretch), then carboxylic acids (O –H bend) and alkanes (C– H) stretching vibrations. The compounds including Hexadecane, Eicosane, Heptadecane, Cyclohexane and Hexadecenoic acid were confirmed using GC-MS analysis. Overall, this result provides the therapeutic roles of secondary metabolites derived from actinobacterial strain and it could be useful for biomedical applications. [ABSTRACT FROM AUTHOR]

Moringa oleifera (MO) has been an important plant for food and traditional medicine in Asian countries, including Indonesia. The leaves of these plants are reported to be rich in antioxidants, vitamins, and micronutrients and have been proven to have nootropic properties. Therefore, we investigated whether MO could provide protective effects on SH‐SY5Y neuroblastoma cells exposed to H2O2. In this study, we observed cotreating water‐extracted MO leaves on the inhibition of reactive oxygen species (ROS). We found that this treatment enhanced the activities of glutathione peroxidase, catalase, and superoxide dismutase. In addition, it suppressed the mRNA expression levels of apoptotic gene‐related genes, specifically Bcl‐2 associated protein X (BAX) and caspase 3. Furthermore, it promoted neuroplasticity by increasing the brain‐derived neurotropic factor (BDNF) mRNA expression in SH‐SY5Y cells. The protein expression of phosphorylated‐Akt and phosphorylated‐CREB, essential genes in neuroplasticity, was also increased in cells treated with H2O2 and MO. Therefore, the neuroprotective effects of MO against oxidative stress are attributed to its antioxidant and antiapoptotic properties, as well as its ability to modify the neuronal signaling pathway. [ABSTRACT FROM AUTHOR]

Candida parapsilosis was introduced as the second most responsible for nail involvement. The colonization of biotic and abiotic surfaces by Candida spp. can result in the formation of biofilms, which possess a high level of resistance to typical antifungal agents. Since Candida spp. can produce biofilm mass on the surface of the nails, dermatologists should consider appropriate antifungals to eliminate both the planktonic and biofilm cells. The aim of this research was to determine the antifungal efficacy of itraconazole against C. parapsilosis sensu lato biofilm formations, in addition to its static effects. Ten C. parapsilosis sensu lato isolates were enrolled in this study. The use of itraconazole results in the accumulation of reactive oxygen species (ROS) during treatment. In order to verify the correlation between ROS and itraconazole-induced cell death, the viability of cells was analyzed by administering the ROS scavenger Ascorbic acid. The apoptotic features of itraconazole were analyzed using the Annexin V-FITC method. Based on current data, it was found that the generation of intracellular stresses by itraconazole is not observed in cells upon ROS inhibition, emphasizing the importance of intracellular ROS in the apoptotic mechanism of itraconazole. Targeting the oxidative defense system is a powerful point to use ROS-inducing antifungals as a superior choice for more effective therapies in case of recalcitrant onychomycosis. [ABSTRACT FROM AUTHOR]

To improve the potential of lupeol against cancer cells, a privileged structure, thiazolidinedione, was introduced into its C-3 hydroxy group with ester, piperazine-carbamate, or ethylenediamine as a linker, and three series of thiazolidinedione-conjugated compounds (6a–i, 9a–i, and 12a–i) were prepared. The target compounds were evaluated for their cytotoxic activities against human lung cancer A549, human breast cancer MCF-7, human hepatocarcinoma HepG2, and human hepatic LO2 cell lines, and the results revealed that most of the compounds displayed improved potency over lupeol. Compound 12i exhibited significant activity against the HepG2 cell line, with an IC50 value of 4.40 μM, which is 9.9-fold more potent than lupeol (IC50 = 43.62 μM). Mechanistic studies suggested that 12i could induce HepG2 cell apoptosis, as evidenced by AO/EB staining and annexin V-FITC/propidium iodide dual staining assays. Western blot analysis suggested that compound 12i can upregulate Bax expression, downregulate Bcl-2 expression, and activate the mitochondria-mediated apoptotic pathway. Collectively, compound 12i is worthy of further investigation to support the discovery of effective agents against cancer. [ABSTRACT FROM AUTHOR]

Retinal degeneration (RD) is a group of ocular diseases characterized by progressive photoreceptor apoptosis and visual impairment. Mitochondrial malfunction, excessive oxidative stress, and chronic activation of neuroglia collectively contribute to the development of RD. Currently, there is a lack of efficacious therapeutic interventions for RD. Stanniocalcin-1 (STC-1) is a promising candidate molecule to decelerate photoreceptor cell death. STC-1 is a secreted calcium/phosphorus regulatory protein that exerts diverse protective effects. Accumulating evidence suggests that STC-1 protects retinal cells from ischemic injury, oxidative stress, and excessive apoptosis through enhancing the expression of uncoupling protein-2 (UCP-2). Furthermore, STC-1 exerts its antiinflammatory effects by inhibiting the activation of microglia and macrophages, as well as the synthesis and secretion of proinflammatory cytokines, such as TNF-α, IL-1, and IL-6. By employing these mechanisms, STC-1 effectively shields the retinal photoreceptors and optic nerve, thereby slowing down the progression of RD. We summarize the STC-1-mediated therapeutic effects on the degenerating retina, with a particular focus on its underlying mechanisms. These findings highlight that STC-1 may act as a versatile molecule to treat degenerative retinopathy. Further research on STC-1 is imperative to establish optimal protocols for its clinical use. [ABSTRACT FROM AUTHOR]

Caspases are enzymes with protease activity. Despite being known for more than three decades, caspase investigation still yields surprising and fascinating information. Initially associated with cell death and inflammation, their functions have gradually been revealed to extend beyond, targeting pathways such as cell proliferation, migration, and differentiation. These processes are also associated with disease mechanisms, positioning caspases as potential targets for numerous pathologies including inflammatory, neurological, metabolic, or oncological conditions. While in vitro studies play a crucial role in elucidating molecular pathways, they lack the context of the body's complexity. Therefore, laboratory animals are an indispensable part of successfully understanding and applying caspase networks. This paper aims to summarize and discuss recent knowledge, understanding, and challenges in caspase knock-out mice. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (Pca) is a deadly disease prevalent among men, and it accounts for about 7–8 % of mortality globally. Synthetic drugs have proved effective but have limitations and severe side effects. There is, therefore, a need to discover a less expensive, natural therapeutic agent with no side effects in treating the ailment. Aim: The study aims to investigate the anti-prostate cancer activity of extracts of Indigofera macrophylla (I. macrophylla) at the physiological and molecular levels in experimental animals. Method: Polyphenol-rich extract of I. macrophylla was subjected to HPLC analysis to identify the plant's phytochemical constituent. Adult Wistar rats were orally administered 2mls of 50, 100 and 200 PPM of the cacodylic acid solution for 28 days to induce prostate cancer, while treatment was carried out by orally administering extract of I. macrophylla at doses of 50, 100 and 200 mg/kg for up to 28 days. The anti-inflammatory and apoptotic properties of the extract in experimental animals were investigated by the expression levels of various genetic biomarkers such as Bax-2, TNF-α, IL-6, COX2, IL-1β, β-Catenin, APC, Bcl2, CEA, Caspase 3 and β-Catenin using reverse transcriptase polymerase chain reaction (RT-PCR). Result: HPLC analysis shows that I. macrophylla has 21 bioactive components which are categorized into seven groups: flavonoid, terpenes, phenols, isoflavonoid, phytosterols, quinone and glycosides. Administration of the drug shows inconsistencies in the mean body weights of the experimental animals. Further investigation revealed that I. macrophylla increased TNF-α upregulation and expression, significantly downregulated IL-1β, significantly decreased IL-6 expression, ameliorated COX2 expression, downregulated β-catenin expression and significantly reduced the expression of the APC gene. These results show that the drug activity modulates the investigated inflammatory and apoptotic genes in the prostate gland of PCa-induced rats, thus demonstrating its anti-PCa potential. Conclusion: The results of this study suggest the potential of a novel treatment protocol of I. macrophylla plant extract to improve therapeutic outcomes for patients with aggressive PCa, which reportedly claims hundreds of thousands of lives yearly.

An FDA-approved kinase inhibitor called sorafenib (SOR) is used to treat primary kidney and liver cancer as well as to stop the spread of advanced breast cancer. Side effects from SOR, such as palmar–plantar erythrodysesthesia syndrome, can negatively impact an individual's quality of life. There are a lot of data supporting the importance of lycopene (LYC) in preventing cancer. The antitumor properties of the combination of sorafenib and lycopene were examined in this study. A viability test against MDA-MB-231 was used to assess the anticancer efficacy of sorafenib, lycopene, and their combination in vitro. Moreover, a cell cycle analysis and Annexin-V/PI double staining were performed by using flow cytometry. In addition, the protein level of JNK-1, ERK-1, Beclin-1, P38, and P53 of the MDA-MB-231 cell line was estimated using ELISA kits. In addition, mice with SEC were divided into four equal groups at random (n = 10) to investigate the possible processes underlying the in vivo antitumor effect. Group IV (SEC-SOR-LYC) received SOR (30 mg/kg/day, p.o.) and LYC (20 mg/kg/day, p.o.); Group I received the SEC control; Group II received SEC-SOR (30 mg/kg/day, p.o.); and Group III received SEC-LYC (20 mg/kg/day, p.o.). The findings demonstrated that the combination of sorafenib and lycopene was superior to sorafenib and lycopene alone in causing early cell cycle arrest, suppressing the viability of cancer cells, and increasing cell apoptosis and autophagy. Likewise, the combination of sorafenib and lycopene demonstrated inhibition of the levels of Bcl-2, Ki-67, VEGF, IL-1β, and TNF-α protein. Otherwise, the quantities of the proteins BAX, P53, and caspase 3 were amplified. Furthermore, the combined treatment led to a substantial increase in TNF-α, caspase 3, and VEGF gene expression compared to the equivalent dosages of monotherapy. The combination of sorafenib and lycopene enhanced apoptosis and reduced inflammation, as seen by the tumor's decreased weight and volume, hence demonstrating its potential anticancer effect. [ABSTRACT FROM AUTHOR]

Abstract The emergence of corona virus disease 2019 (COVID-19), resulting from Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has left an indelible mark on a global scale, causing countless infections and fatalities. This investigation delves into the role of the SARS-CoV-2 nucleocapsid (N) protein within the HEK293 cells, shedding light on its influence over apoptosis, interferon signaling, and cytokines production. The N gene was amplified, inserted into the pAdTrack-CMV vector, and then transfected to the HEK293 cells. Changes in the expression of IRF3, IRF7, IFN-β, BAK, BAX, and BCL-2 genes were evaluated. The levels of proinflammatory cytokines of IL-6, IL-12, IL-1β, and TNF-α were also determined. The N protein exhibited an anti-apoptotic effect by modulating critical genes associated with apoptosis, including BAK, BAX, and BCL-2. This effect potentially prolonged the survival of infected cells. The N protein also played a role in immune evasion by suppressing the interferon pathway, evidenced by the downregulation of essential interferon regulatory factors of IRF3 and IRF7, and IFN-β expression. The N protein expression led to a substantial increase in the production of proinflammatory cytokines of IL-6, IL-12, IL-1β, and TNF-α. The N protein emerged as a versatile factor and was exerted over apoptosis, interferon signaling, and cytokine production. These findings carry potential implications for the development of targeted therapies to combat COVID-19 and mitigate its global health impact.

To improve the potential of lupeol against cancer cells, a privileged structure, thiazolidinedione, was introduced into its C-3 hydroxy group with ester, piperazine-carbamate, or ethylenediamine as a linker, and three series of thiazolidinedione-conjugated compounds (6a–i, 9a–i, and 12a–i) were prepared. The target compounds were evaluated for their cytotoxic activities against human lung cancer A549, human breast cancer MCF-7, human hepatocarcinoma HepG2, and human hepatic LO2 cell lines, and the results revealed that most of the compounds displayed improved potency over lupeol. Compound 12i exhibited significant activity against the HepG2 cell line, with an IC50 value of 4.40 μM, which is 9.9-fold more potent than lupeol (IC50 = 43.62 μM). Mechanistic studies suggested that 12i could induce HepG2 cell apoptosis, as evidenced by AO/EB staining and annexin V-FITC/propidium iodide dual staining assays. Western blot analysis suggested that compound 12i can upregulate Bax expression, downregulate Bcl-2 expression, and activate the mitochondria-mediated apoptotic pathway. Collectively, compound 12i is worthy of further investigation to support the discovery of effective agents against cancer.

Background/aim: Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer. The critical importance of circular RNA (circRNA) in a range of cancer types has been lately recognized. However, research on the functions of circRNAs in PTC has been limited thus far. Therefore, this research aimed at exploring the function and mechanism of circ-methyltransferase-like 15 (METTL15) in PTC cells. Materials and methods: Quantitative measurements of circ-METTL15, miR-200c-3p, and X-linked inhibitor of apoptosis protein (XIAP) in PTC cells were conducted using reverse transcription-quantitative polymerase chain reaction or Western blot analysis. To investigate cell growth, cell counting kit-8 and colony formation tests were employed, apoptosis was analyzed using flow cytometry, and migration and invasion were studied through Transwell assays. The targeted binding sites between miR-200c-3p and circ-METTL15 or XIAP were predicted by starBase and then verified by dual luciferase reporter assay. Results: circ-METTL15 and XIAP were upregulated in the PTC cells, while miR-200c-3p was downregulated. Downregulating circ- METTL15 or upregulating miR-200c-3p resulted in inhibited proliferation, migration, and invasion of PTC cells, while promoting apoptosis. miR-200c-3p was the downstream molecule of circ-METTL15, and XIAP was the direct target of miR-200c-3p. Forcing XIAP expression obstructed circ-METTL15 silencing to inhibit PTC cell activity. Conclusion: By coopting miR-200c-3p/XIAP, Circ-METTL15 stimulates aggressive behavior in PTC cells. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2  weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5  days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV. [ABSTRACT FROM AUTHOR]

The present study evaluated the synthesis of iron oxide nanoparticles using Spermacoce ocymoides Burm.f. plant extracts, and the effects of plant based iron oxide nanoparticles on A549 lung cancer cells were investigated to elucidate their impact on cellular morphology, mitochondrial function, and apoptotic pathways. Spermacoce ocymoides plant based iron oxide nanoparticles were characterised by X-ray diffraction, Atomic force microscopy, FTIR, and UV-Vis absorption spectroscopy. Iron oxide nanoparticle treatment caused considerable morphological alterations in A549 cells, including cell shrinkage, detachment, membrane blabbing, and distorted shape, consistent with cellular stress and potential apoptotic events. MMP analysis revealed a dose-dependent decrease in mitochondrial membrane potential, implying that nanoparticles have an effect on mitochondrial function. The presence of reactive oxygen species suggested that oxidative stress was involved in the cellular response to iron oxide nanoparticles. Additionally, DNA fragmentation analysis confirmed the activation of apoptotic pathways, with the nanoparticles themselves serving as a positive control for inducing apoptosis. The observed morphological changes, altered mitochondrial function, ROS production, and DNA fragmentation collectively point towards apoptotic cell death pathways being triggered by the nanoparticles. [ABSTRACT FROM AUTHOR]

Surgery, chemotherapy, and radiation therapy are all forms of cancer treatment, as well as more recent methods including interventional radiology and immunotherapy. In this study, we synthesize a novel chitosan (CH) nanocomplex (NC)-based polysaccharide Krestin (PSK) for drug delivery. This technique was used to develop PSK@CH@NC. According to the study, PSK@CH@NC had a particle size of around 500 nm, slight polydispersity as observed under a scanning electron microscope, and a strong positive surface charge of 18 mV. Investigation into the in vitro growth inhibition of the MCF-7 cell line after treatment with CH, PSK, and PSK@CH@NC was followed by morphological changes. Compared to other treatment groups, PSK@CH@NC therapy dramatically reduced the fraction of apoptotic cells, cancer cell survival, and proliferation. Fluorescence analysis was used to examine how PSK@CH@NC affected the distribution of cell cycle phases. This study also shows that a promising foundation for creating cancer nanomedicine can be established by employing new polysaccharides.

AbstractContext Xiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear.Objective To investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms.Materials and methods C57BL/6 mice were randomized into six groups (n = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed.Results The results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa.Discussion and conclusions XJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent.

Cancer is one of the most common pathologies in the world, leading to a reduced standard of living and even death for centuries. Despite promising developments in treatment methods in recent years, the expected level of treatment and success hasn’t yet been achieved due to the side effects and cost of treatment methods and the fact that some drugs are still in the trial phase. This situation has encouraged the scientific community to search for natural agents with lower costs and limited side effects. Abies cilicica, also known as fir, and Aloe vera has been used in both food and traditional medicine from the past to the present. In the literature review, it was found that both A. vera and A. cilicica have many beneficial effects, especially anti-inflammatory, antifungal, and wound-healing properties. This study aimed to investigate the antimicrobial, antioxidant, cytotoxic, and apoptotic/necrotic effects of extracts of A. vera from Asphodelaceae and A. cilicica (Ant. Et Kotschy.) subsp. cilicica Carr. from Pinaceae. The best antimicrobial activity was observed against Escerichia coli with a zone diameter of 20.00 ± 3.59 mm and Klebsiella pneumoniae with a zone diameter of 21 ± 5.35 mm. 2KA showed the best effect on antioxidant activity. 2MA + 2KSA showed significant cytotoxic activity on MDA-MB-231 cancer cells. IC50 values of 1EA + 1KA extract (whole A. cilicica and A. vera dissolved in ethanol) against MDA-MB-231 cell line (IC50 458.29 ± 19.01 µg/ml) and MCF-7 cell line (IC50 596.03 ± 5.56 µg/ml) were determined. According to the data obtained from the study, A. vera and A. cilicica were found to have antimicrobial, antioxidant, and cytotoxic effects both alone and synergistically. It is predicted that they can be used especially in cancer treatment.

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV.

Background and Aims: Hepatic ischaemia/reperfusion injury (HIRI) is a pathophysiological process that occurs during the liver resection and transplantation. Reportedly, peroxisome proliferator‐activated receptor β/δ (PPARβ/δ) can ameliorate kidney and myocardial ischaemia/reperfusion injury. However, the effect of PPARβ/δ in HIRI remains unclear. Methods: Mouse hepatic ischaemia/reperfusion (I/R) models were constructed for in vivo study. Primary hepatocytes and Kupffer cells (KCs) isolated from mice and cell anoxia/reoxygenation (A/R) injury model were constructed for in vitro study. Liver injury and inflammation were investigated. Small molecular compounds (GW0742 and GSK0660) and adenoviruses were used to interfere with PPARβ/δ. Results: We found that PPARβ/δ expression was increased in the I/R and A/R models. Overexpression of PPARβ/δ in hepatocytes alleviated A/R‐induced cell apoptosis, while knockdown of PPARβ/δ in hepatocytes aggravated A/R injury. Activation of PPARβ/δ by GW0742 protected against I/R‐induced liver damage, inflammation and cell death, whereas inhibition of PPARβ/δ by GSK0660 had the opposite effects. Consistent results were obtained in mouse I/R models through the tail vein injection of adenovirus‐mediated PPARβ/δ overexpression or knockdown vectors. Furthermore, knockdown and overexpression of PPARβ/δ in KCs aggravated and ameliorated A/R‐induced hepatocyte injury, respectively. Gene ontology and gene set enrichment analysis showed that PPARβ/δ deletion was significantly enriched in the NF–κB pathway. PPARβ/δ inhibited the expression of p‐IKBα and p‐P65 and decreased NF–κB activity. Conclusions: PPARβ/δ exerts anti‐inflammatory and anti‐apoptotic effects on HIRI by inhibiting the NF–κB pathway, and hepatocytes and KCs may play a synergistic role in this phenomenon. Thus, PPARβ/δ is a potential therapeutic target for HIRI. [ABSTRACT FROM AUTHOR]

Xiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear. To investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms. C57BL/6 mice were randomized into six groups (n = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed. The results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa. XJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is a frequently used therapeutic modality for breast cancer. Dalbergin, a natural antioxidant, inhibits carcinogens and tumor progression. In the present study, we investigated the effect of Dalbergin on the response of T47D and MDA-MB-231 breast cancer cell lines to ionizing radiation.Method: In this experimental in vitro study, doubling time of T47D and MDAMB- 231 were obtained from the growth curve. The cytotoxic effect of Dalbergin on T47D and MDA-MB-231 breast cancer cells were estimated via MTT assay. To determine the clonogenic ability, we treated T47D and MDA-MB-231 with Dalbergin for 48 h prior to irradiation, subsequent to which a colony assay was performed. Real-time polymerase chain reaction was employed to determine the gene expression level.Results: Dalbergin inhibited proliferation of T47D and MDA-MB-231 in a time and concentration-dependent manner. Additionally, the most appropriate time for the treatment of these types of cancer cells was found to be 48 h and the drug's concentration in both cell lines was different. The IC50 values of T47D and MDA-MB-231 cells were 0.001 and 0.0001 μM, respectively. Moreover, this drug radiaosensitizes both cell lines effectively compared with the radiation only. Finally, the gene expression level of p53, Bcl-2, and STAT3 were investigated in cancer cells.Conclusion: Dalbergin showed apoptotic effects probably through the STAT/p53 signaling pathway. Therefore, Dalbergin could be considered as a radiosensitizer and its effects may be owing to increased cell death.

An FDA-approved kinase inhibitor called sorafenib (SOR) is used to treat primary kidney and liver cancer as well as to stop the spread of advanced breast cancer. Side effects from SOR, such as palmar–plantar erythrodysesthesia syndrome, can negatively impact an individual’s quality of life. There are a lot of data supporting the importance of lycopene (LYC) in preventing cancer. The antitumor properties of the combination of sorafenib and lycopene were examined in this study. A viability test against MDA-MB-231 was used to assess the anticancer efficacy of sorafenib, lycopene, and their combination in vitro. Moreover, a cell cycle analysis and Annexin-V/PI double staining were performed by using flow cytometry. In addition, the protein level of JNK-1, ERK-1, Beclin-1, P38, and P53 of the MDA-MB-231 cell line was estimated using ELISA kits. In addition, mice with SEC were divided into four equal groups at random (n = 10) to investigate the possible processes underlying the in vivo antitumor effect. Group IV (SEC-SOR-LYC) received SOR (30 mg/kg/day, p.o.) and LYC (20 mg/kg/day, p.o.); Group I received the SEC control; Group II received SEC-SOR (30 mg/kg/day, p.o.); and Group III received SEC-LYC (20 mg/kg/day, p.o.). The findings demonstrated that the combination of sorafenib and lycopene was superior to sorafenib and lycopene alone in causing early cell cycle arrest, suppressing the viability of cancer cells, and increasing cell apoptosis and autophagy. Likewise, the combination of sorafenib and lycopene demonstrated inhibition of the levels of Bcl-2, Ki-67, VEGF, IL-1β, and TNF-α protein. Otherwise, the quantities of the proteins BAX, P53, and caspase 3 were amplified. Furthermore, the combined treatment led to a substantial increase in TNF-α, caspase 3, and VEGF gene expression compared to the equivalent dosages of monotherapy. The combination of sorafenib and lycopene enhanced apoptosis and reduced inflammation, as seen by the tumor’s decreased weight and volume, hence demonstrating its potential anticancer effect.

One of the most essential health problems is cancer, the first or second cause of death worldwide. Head and neck cancers are hard to detect due to non-specific symptoms. The treatment often relies on a combination of radio and chemotherapy. For this reason, the research of new anticancer compounds is fundamental. The natural and synthetic compounds with 1,4-naphthoquinone scaffold is characterized by high anticancer activity. The study aimed to evaluate the synthesis and anticancer activity of hybrids 1,4-naphthoquinone with thymidine derivatives. The series of compounds allows us to check the influence of the substituent in the C3′ position of the thymidine moiety on the cytotoxicity against squamous cancer cell lines (SCC-9 and SCC-25) and submandibular gland cancer (A-253). An annexin V/propidium iodide (PI) co-staining assay shows that derivatives cause the apoptotic in SCC-25 and A-253 cell lines. The molecular docking study examined the interaction between the active site of the BCL-2 protein and the hybrids. [ABSTRACT FROM AUTHOR]

Simple Summary: Semen cryopreservation is a reliable technique used in artificial reproduction technology to preserve and transmit buffaloes' superior genetic qualities. Buffalo sperm cells are highly susceptible to cryopreservation due to the abundant polyunsaturated fatty acids in their plasma membrane. The use of nanoparticles in freezing extenders is one of the most recent techniques for reducing the detrimental effects of cryopreservation on the post-thawed quality of buffalo spermatozoa. In this study, thymoquinone nanoparticles (TQNPs) were used for the first time as an effective method to enhance the sperm quality and fertilizing ability of frozen–thawed buffalo sperm. The addition of optimal levels of TQNPs (25 to 50 µg/mL) improved post-thawed sperm parameters and sperm kinematics, as well as maintained the morphology of sperm by supporting the total antioxidant capacity and reducing membrane damage, apoptotic sperm, and oxidative stress-related markers. These data can provide a novel nanotechnology-based strategy for enhancing the cryopreservation efficiency of buffalo sperm. Thymoquinone nanoparticles (TQNPs) are broadly utilized in numerous pharmaceutical applications. In the present study, we tested the effects of TQNP supplementation on sperm quality and kinematics, acrosome exocytosis, oxidative biomarkers, apoptosis-like and morphological changes of frozen–thawed buffalo sperm, as well as the fertilizing capacity. Semen was collected from buffalo bulls, diluted (1:10; semen/extender), and divided into five aliquots comprising various concentrations of TQNP 0 (CON), 12.5 (TQNP12.5), 25 (TQNP25), 37.5 (TQNP37.5), and 50 (TQNP50) µg/mL, and then cryopreserved and stored in liquid nitrogen (−196 °C). The results revealed that TQNPs (25 to 50 µg/mL) provided the most optimal results in terms of membrane integrity (p < 0.001) and progressive motility (p < 0.01). In contrast, TQNP50 resulted in a greater post-thawed sperm viability (p = 0.02) compared with other groups. The addition of TQNPs to the extender had no discernible effects on sperm morphology measures. Sperm kinematic motion was significantly improved in the TQNP50 group compared to the control group (p < 0.01). TQNPs effectively reduced the content of H2O2 and MDA levels and improved the total antioxidant capacity of post-thawed extended semen (p < 0.01). The addition of TQNP significantly increased the number of intact acrosomes (p < 0.0001) and decreased the number of exocytosed acrosomes (p < 0.0001). A significant reduction in apoptosis-like changes was observed in TQNP groups. The non-return rates of buffalo cows inseminated with TQNP50-treated spermatozoa were higher than those in the control group (p < 0.05; 88% vs. 72%). These findings suggested that the freezing extender supplemented with TQNPs could effectively enhance the cryotolerance and fertility of buffalo sperm. [ABSTRACT FROM AUTHOR]

This study was done of green synthesized zinc oxide nanoparticles (ZnO NPs) by using flaxseed extract (Linum usitatissimum L.) and investigated their potential anticancer effects. The ZnO NPs were characterized by UV–Vis, SEM/EDS, and XRD techniques. These analyses showed that these NPs were spherically shaped with a 23–55 nm size range. The cytotoxicity of NPs was confirmed by MTT assay against A549, HT29, and MDA-MB-231 cancer cells, indicating their antiproliferative effect (IC50 values: 68.3, 66.3, and 58.8 μg/mL, respectively). The apoptotic induction was analyzed by ELISA, and the results showed that the NPs induced apoptosis through caspase-3/9 activation but not by caspase-8. These NPs significantly trigger the intrinsic-apoptotic pathway. Moreover, they exhibited strong antimigratory properties on the lowly metastatic HT29 and the highly metastatic A549 and MDA-MB-231 cells. This is the first report of Linum usitatissimum L-mediated synthesis of ZnO NPs that could be considered as potential antineoplastic agents. [ABSTRACT FROM AUTHOR]

Tyrosol (TYR) and parthenolide (PLT) have been used as synthetic antioxidant and natural anticancer compounds. In the current study, we aimed to synthesize an encapsulated complex of both PLT and TYR in a hybrid coating layer consisting of lecithin and chitosan molecules, a proper biocompatible drug delivery system to evaluate its antibacterial and anticancer potentials on human liver HepG2 and pancreatic Panc cancer cell lines. The chitosan-lecithin-coated PLT/TYR nanoparticles (clPT-NPs) were synthesized applying an auto-self-assembling method. The clPT-NPs were characterized utilizing DLS, FTIR, zeta potential, and TEM analysis. The clPT-NPs' antioxidant activity was measured by running ABTS and DPPH antioxidant assays. Moreover, the antibacterial potential of clPT-NPs was evaluated by applying disk diffusion, MIC, and MBC assays. Finally, the nanoparticles' cytotoxicity and apoptotic activity were studied by conducting MTT, Flow cytometry, AO/PI cell staining, and real-time PCR techniques. The clPT-NPs (38 nm) exhibited significant antioxidant activity by inhibiting ABTS and DPPH radicals at 187 and 290 μg/mL IC50 concentrations, respectively. Also, the nanoparticles induced a notable antibacterial activity against Staphylococcus aureus at 0.0625 mg/mL MIC and 0.125 mg/mL MBC concentrations. The clPT-NPs selectively decreased the cancer cells' survival and increased the apoptotic dead cells by up-regulating apoptotic gene expression (BAX and Cas-8) and down-regulating BCL-2 anti-apoptotic gene expression. The PLT toxicity has been merged with improved TYR antioxidant activity, which has been functionalized in a safe, biocompatible hybrid nano-delivery system. [ABSTRACT FROM AUTHOR]

Colon cancer is one of the most common types of cancer worldwide, and its incidence is increasing. Despite advances in medical science, the treatment of colon cancer still poses a significant challenge. This study aimed to investigate the potential protective effects of Adiantum pedatum (AP) extract and/or piceatannol on colon cancer induced via phenylhydrazine (PHZ) in terms of the antioxidant and apoptotic pathways and histopathologic changes in the colons of male albino rats. The rats were randomly divided into eight groups: control, AP extract, piceatannol (P), PHZ, PHZ and AP treatments, PHZ and P treatments, PHZ and both AP and P, and PHZ and prophylaxis with both AP and P. The results demonstrated that PHZ induced oxidative damage, apoptosis, and histopathological changes compared to the control group. However, the administration of AP or P or AP + P as therapy or prophylaxis significantly ameliorated these changes and upregulated the colonic mir-145 and mRNA expression of P53 and PDCD-4 while downregulating the colonic mRNA expression of PI3K, AKT, c-Myc, CK-20, SOX-2, OCT-4, and NanoG compared to the PHZ group. These findings suggest that the candidate drugs may exert their anti-cancer effects through multiple mechanisms, including antioxidant and apoptotic activities. [ABSTRACT FROM AUTHOR]

Scutellaria multicaulis is a medicinal plant indigenous to Iran, Afghanistan, and Pakistan. It has been widely used as a prominent herb in traditional medicine for thousands of years. This plant is reported to contain baicalein, wogonin, and chrysin flavonoids, which are a significant group of chemical ingredients which can cure different diseases, such as breast cancer. S. multicaulis leaf extract was used for the bioreduction of silver nanoparticles (SmL-Ag-NPs), and their phytochemical contents and antioxidant, antibacterial, anti-proliferative, and apoptotic activity were evaluated. Optimal physicochemical properties of SmL-Ag-NPs were obtained by mixing 5% of leaf extract and 2 mM of aqueous AgNO3 solution and confirmed by characterization studies including UV–visible spectrophotometry, Field Emission Scanning Electron Microscope (FE-SEM), Energy Dispersive X-ray (EDX), Dynamic Light Scattering (DLS), zeta potential, Thermogravimetric analysis (TGA), Surface-enhanced Raman spectroscopy (SERS), X-ray crystallography (XRD), and Fourier transform infrared (FTIR) Spectroscopy. SmL-Ag-NPs exhibited a higher content of total phenol and total flavonoid and potential antioxidant activity. SmL-Ag-NPs also demonstrated dose-dependent cytotoxicity against MDA-MB231 cell multiplication with an IC50 value of 37.62 μg/mL through inducing cell apoptosis. Results show that SmL-Ag-NPs is effective at inhibiting the proliferation of MDA-MB231 cells compared to tamoxifen. This demonstrates that SmL-Ag-NPs could be a bio-friendly and safe strategy to develop new cancer therapies with a reduction in the adverse effects of chemotherapy in the near future. [ABSTRACT FROM AUTHOR]

Cancer is one of the most common pathologies in the world, leading to a reduced standard of living and even death for centuries. Despite promising developments in treatment methods in recent years, the expected level of treatment and success hasn't yet been achieved due to the side effects and cost of treatment methods and the fact that some drugs are still in the trial phase. This situation has encouraged the scientific community to search for natural agents with lower costs and limited side effects. Abies cilicica, also known as fir, and Aloe vera has been used in both food and traditional medicine from the past to the present. In the literature review, it was found that both A. vera and A. cilicica have many beneficial effects, especially anti-inflammatory, antifungal, and wound-healing properties. This study aimed to investigate the antimicrobial, antioxidant, cytotoxic, and apoptotic/necrotic effects of extracts of A. vera from Asphodelaceae and A. cilicica (Ant. Et Kotschy.) subsp. cilicica Carr. from Pinaceae. The best antimicrobial activity was observed against Escerichia coli with a zone diameter of 20.00 ± 3.59 mm and Klebsiella pneumoniae with a zone diameter of 21 ± 5.35 mm. 2KA showed the best effect on antioxidant activity. 2MA + 2KSA showed significant cytotoxic activity on MDA-MB-231 cancer cells. IC50 values of 1EA + 1KA extract (whole A. cilicica and A. vera dissolved in ethanol) against MDA-MB-231 cell line (IC50 458.29 ± 19.01 µg/ml) and MCF-7 cell line (IC50 596.03 ± 5.56 µg/ml) were determined. According to the data obtained from the study, A. vera and A. cilicica were found to have antimicrobial, antioxidant, and cytotoxic effects both alone and synergistically. It is predicted that they can be used especially in cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common and aggressive type of liver cancer. Most chemotherapeutic medications nowadays imply oxidative stress leading to toxicity, which causes the necessity to find agents with better safety profiles against normal cells in addition to their anticancer activity. Sitagliptin has been shown to possess antioxidant as well as apoptotic properties by the specific suppression of dipeptidyl-peptidase 4, a glycoprotein produced in many tissues that have been thought to promote tumorigenesis and metastasis. Methods: Five groups of cell lines were included: Control (untreated HepG2 cells); cisplatin treatment HepG2 cells; sitagliptin treated HepG2 cells; combination of different concentrations of cisplatin plus sitagliptin (250 μg/mL) treated HepG2 cells, and finally, combination of different concentrations of sitagliptin plus cisplatin (25 μg/mL)-treated HepG2 cells. After an incubation period for 48 hours, the supernatants were collected to quantify the level malondialdehyde (MDA) and B-cell lymphoma-2 (BCL-2) by ELISA assay kits. Data were finally gathered and analyzed statistically. Results: Our findings indicated that sitagliptin significantly decreased the oxidative stress, particularly at high concentrations, through decreasing the MDA level. In addition, sitagliptin exhibited significant apoptotic activity against HepG2 cells through decreasing BCL-2 level. In combination with cisplatin, sitagliptin significantly potentiated the apoptotic effect and reduced the oxidative stress parameters. Conclusions: Sitagliptin showed apoptotic and antioxidant activity against HCC which may potentiate chemotherapeutic agents like cisplatin, in addition to reducing the oxidative stress against normal cells.

Abstract Background Oral cancer, one of the most common cancers, has unimproved 5-years survival rate in the last 30 years and the chemo/radiotherapy-associated morbidity. Therefore, intervention strategies that evade harmful side effects of the conventional treatment modalities are of need. Herbal therapy as a complementary preventive/therapeutic modality has gained attention. Curcumin is one of the herbal compounds possessing unique anticancer activity and luminescent optical properties. However, its low water solubility limits its efficacy. In contrast, curcumin at the nanoscale shows altered physical properties with enhancing bioavailability. Methods The current study evaluated the impact of nanocurcumin as an anti-oral cancer herbal remedy, comparing its efficacy against the native curcumin complement and conventional chemotherapeutic. An optimized polymeric-stabilized nanocurcumin was synthesized using the solvent-antisolvent precipitation technique. After assuring the solubility and biocompatibility of nanocurcumin, we determined its cytotoxic dose in treating the squamous cell carcinoma cell line. We then evaluated the anti-tumorigenic activity of the nano-herb in inhibiting wound closure and the cytological alterations of the treated cancer cells. Furthermore, the cellular uptake of the nanocurcumin was assessed depending on its autofluorescence. Results The hydrophilic optimized nanocurcumin has a potent cancerous cytotoxicity at a lower dose (60.8 µg/mL) than the native curcumin particles (212.4 µg/mL) that precipitated on high doses hindering their cellular uptake. Moreover, the nanocurcumin showed differential targeting of the cancer cells over the normal fibroblasts with a selectivity index of 4.5. With the confocal microscopy, the luminescent nanoparticles showed gradual nuclear and cytoplasmic uptake with apparent apoptotic cell death, over the fluorescent doxorubicin with its necrotic effect. Furthermore, the nanocurcumin superiorly inhibited the migration of cancer cells by -25%. Conclusions The bioavailable nanocurcumin has better apoptotic cytotoxicity. Moreover, its superior luminescence promotes the theranostic potentialities of the nano-herb combating oral cancer.

The utilization of ceramides, which are members of the sphingolipid family, has been widely acknowledged in the cosmetic and pharmaceutical industries, along with various other applications as therapeutic agents. Most ceramides currently available on the market are synthetic ceramides created through chemical reactions with precursors resembling the natural precursor of sphingolipid production by living organisms. In fact, many organisms ranging from microbes to higher-order mammals natively use metabolism to produce sphingolipids, including ceramides and their derivatives, to support cell molecular functions. Sphingolipids, for instance, are present in the cell membranes of mammals, plants, and yeast to maintain membrane morphology. As a green alternative to the chemical synthesis method, many studies have been carried out to reveal the diversity and characteristics of biologically produced ceramide derivatives. In this review, we summarized the most important aspects of ceramide biosynthesis in general and provide a quick overview of the common organisms producing ceramides. In addition, a brief discussion regarding the role of ceramides in cells and their risks was included. As the biosynthesis of ceramides is an attractive alternative to current commercial methods, the advances reviewed herein demonstrate the untapped potential for the further development of synthetic pathways to enhance biobased-ceramide production. [ABSTRACT FROM AUTHOR]

Calcitriol, a biologically active metabolite of vitamin D, regulates signaling pathways related to proliferation, malignant transformation, invasion, metastasis, angiogenesis, and inflammation in human cells. In that context, it is crucial to determine anticancer effects of calcitriol in terms of preventing the development of breast cancer, which is the most common malignancy in women, and improving its prognosis. Here, we investigated possible anti-inflammatory, antitumoral, antiproliferative, and proapoptotic effects of various doses of calcitriol that we applied in vitro conditions on breast adenocarcinoma (MCF-7) and healthy breast epithelial cell lines (MCF-10A). We treated cell lines with 0.5, 1, 10, 25, 50, 100, 200, 500, 1000 and 10000 nM doses of calcitriol for 24 and 48 h. After exposure of 100 nM calcitriol to MCF-7 cell line for 24 h, a significant decrease in cell viability, a significant increase in apoptosis rate, a 13-fold increase in the vitamin D receptor (VDR), a 3-fold decrease in NF-κB, an 8-fold decrease in PGE2, and a 1.5-fold decrease in COX-2 expression levels were detected compared to the control group. Further, it was determined that a 100 nM dose of calcitriol had antiproliferative, anti-inflammatory, apoptosis-inducing and tumor suppressive effects on MCF-7 breast adenocarcinoma cell line. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is a frequently used therapeutic modality for breast cancer. Dalbergin, a natural antioxidant, inhibits carcinogens and tumor progression. In the present study, we investigated the effect of Dalbergin on the response of T47D and MDA-MB-231 breast cancer cell lines to ionizing radiation. Method: In this experimental in vitro study, doubling time of T47D and MDA-MB-231 were obtained from the growth curve. The cytotoxic effect of Dalbergin on T47D and MDA-MB-231 breast cancer cells were estimated via MTT assay. To determine the clonogenic ability, we treated T47D and MDA-MB-231 with Dalbergin for 48 h prior to irradiation, subsequent to which a colony assay was performed. Realtime polymerase chain reaction was employed to determine the gene expression level. Results: Dalbergin inhibited proliferation of T47D and MDA-MB-231 in a time-and concentration-dependent manner. Additionally, the most appropriate time for the treatment of these types of cancer cells was found to be 48 h and the drug's concentration in both cell lines was different. The IC50 values of T47D and MDA-MB-231 cells were 0.001 and 0.0001 μM, respectively. Moreover, this drug radiaosensitizes both cell lines effectively compared with the radiation only. Finally, the gene expression level of p53, Bcl-2, and STAT3 were investigated in cancer cells. Conclusion: Dalbergin showed apoptotic effects probably through the STAT/p53 signaling pathway. Therefore, Dalbergin could be considered as a radiosensitizer and its effects may be owing to increased cell death. [ABSTRACT FROM AUTHOR]

Background: Endometriosis has a major impact on women’s quality of life. The two primary pathologies are chronic inflammation and altered apoptotic activity. Sulawesi propolis has been shown to have known anti-inflammatory and pro-apoptotic properties in other diseases. Objective: To investigate the effects of Sulawesi propolis in the rat endometriosis model. Methods: An autologous endometriosis model was created in 60 female Wistar rats by laparotomy. Rats were divided into four groups (n = 15 in each group): control group (CG), dienogest group (DG), propolis 50 mg/kg body weight (BW)/day (P50) group, and propolis 100 mg/kg BW/day (P100) group. Each treatment group was divided into three different treatment durations (n = 5 in each treatment group): 2, 4 and 6 weeks. After treatment, laparotomy was performed to determine endometriotic tissue growth, apoptosis [caspase-3 and Bcl-2-associated X/Bcl-2 (Bax/Bcl)] and inflammation [prostaglandin-E2 (PGE2) and interleukin-1B (IL-1B)]. Results: A significant difference was seen in endometriotic tissue growth between the P50 group and the CG, with the greatest reduction in the P50 6-week (P50–6) group, reaching 70.66% of the initial area. Highest Bax/Bcl-2 mRNA expression was shown in the P50–4 and P100–4 groups, highest caspase-3 expression was shown in the P50–2 and P50–4 groups, and lowest IL-1B expression was shown in the P50–4 group; all differed significantly from the CG. No significant difference in PGE2S mRNA was found between the groups. Conclusion: Sulawesi propolis extract suppressed endometriotic tissue growth in the rat model by increasing apoptotic activity. The effects were time-dependent, with 50 mg/kg BW as the optimal dose.

Background: Kinesin family member 15 (KIF15) is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers. However, the role of KIF15 in the development of nasopharyngeal cancer (NPC) is still unclear. Methods: The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus (GEO) database and immunohistochemical analysis of clinical specimens collected from a patient cohort. Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15-knockdown cell models. CCK8 assay, flow cytometry, wound healing, Transwell and clone formation assays were used to detect the proliferation, apoptosis, migration, invasion and colony formation of NPC cells in vitro. A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study. Furthermore, the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis, and several in vitro and in vivo functional assays were performed to explore its role in NPC. Results: The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues. High levels of KIF15 expression were also associated with short overall survival (OS) and progression-free survival (PFS). Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2 (G2) phase, inhibition of cell proliferation, migration, invasion, colony formation, and enhanced cell apoptosis. The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC. Moreover, the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC. Rescue assays indicated that Pifithrin-α could counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15. Conclusion: This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases. Therefore, KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC. [ABSTRACT FROM AUTHOR]

Diazinon (DZN) is an organophosphate insecticide that has been globally used in agriculture and domestic areas for several years, leading to a variety of negative effects in different targets of humans. This study focused on evaluating the kidney protective role of resveratrol (Res) against sub-chronic DZN exposure by estimating oxidative, anti-oxidative, inflammatory, and apoptotic markers, along with renal function indexes. Overall, 30 Wistar rats were randomly divided into five groups. Groups 1 (control group), 2, 3, 4, and 5 received corn oil, DZN (70 mg/kg), DZN (70 mg/kg) plus Res 5 mg/kg, DZN (70 mg/kg) plus Res 10 mg/kg, and DZN (70 mg/kg) plus Res 20 mg/kg orally, respectively. DZN increased the serum and kidney level of malondialdehyde, total oxidant status, tumor necrosis factor-α (TNF-α), and the expression ratio of Fox-1 and Bax-2. On the other hand, DZN decreased the serum and kidney level of of Total Antioxidant Capacity (TAC), Superoxide dismutase (SOD), Catalase activities (CAT), and the expression ratio of Forkhead box protein O1 (Foxo1); sirtuin 1(Sirt-1);. Based on the results, blood urea nitrogen (BUN) and creatinine (Cr) as the kidney function index were notably changed in all groups. Res treatment inversed DZN-induced kidney toxicity, Finally, Res improved DZN-induced kidney histopathological changes. Overall, these results first demonstrated that Res has protective effects on renal toxicities induced by DZN. [ABSTRACT FROM AUTHOR]

Colon cancer etiology involves a wide spectrum of genetic and epigenetic alterations, finding it challenging to find effective therapeutic strategies. Quercetin exhibits potent anti-proliferative/apoptotic properties. In the present study, we aimed to elucidate the anti-cancer and anti-aging effect of quercetin in colon cancer cell lines. The anti-proliferative effect of quercetin was assessed in vitro by CCK-8 in normal and colon cancer cell lines. To check the anti-aging potential of quercetin, collagenase, elastase, and hyaluronidase inhibitory activity assays were performed. The epigenetic and DNA damage assays were performed using the human NAD-dependent deacetylase Sirtuin-6, proteasome 20S, Klotho, Cytochrome-C, and telomerase ELISA kits. Furthermore, the aging-associated miRNA expression profiling was performed on colon cancer cells. The treatment with quercetin inhibited cell proliferation of colon cancer cells in a dose-dependent manner. Quercetin arrested colon cancer cell growth by modulating expression of aging proteins including Sirtuin-6 and Klotho and also by inhibiting telomerase activity to restrict the telomere length which is evident from qPCR analysis. Quercetin also exhibited DNA damage protection by reducing proteasome 20S levels. The miRNA expression profiling results displayed differential expression of miRNA in colon cancer cell, and in addition, the highly upregulated miRNA was involved in the regulation of cell cycle, proliferation, and transcription. Our data suggest that quercetin treatment inhibited cell proliferation in colon cancer cells through regulating the anti-aging protein expression and provides better understanding for quercetin’s potential use in colon cancer treatment. [ABSTRACT FROM AUTHOR]

Autoimmune thyroiditis (AIT) has a complex aetiology and the susceptibility to it is determined by a combination of genetic and environmental factors, although these are not yet fully understood. The present research aimed to explore the DNA methylation patterns in whole blood of extrinsic apoptotic signalling pathway-related genes in AIT among areas with different iodine levels. We selected the iodine-fortification areas, iodine-adequate areas and water-based iodine-excess areas from Shandong Province of China as survey sites. Totally, 176 AIT cases and 176 controls were included. MethylTargetTM and QT-PCR technology were used to detect candidate genes' DNA methylation levels and mRNA expression levels, respectively. We found that death associated protein kinase 1 (DAPK1) DNA methylation levels in AIT cases (especially in female) were significantly higher than controls (t = 2·7715, P = 0·0059; t = 2·4638, P = 0·0143 in female). There were differences in DAPK1 (t = 2·5384, P = 0·0121), TNF superfamily member 8 (t = 2·1667, P = 0·0334) and TNF- α -induced protein 8 (TNFAIP8) (t = 2·5672, P = 0·0121) genes methylation between cases and controls with different water iodine levels. The mRNA expression of DAPK1 (t = 4·329, P < 0·001) and TNFAIP8 (t = 3·775, P < 0·001) in the cases was increased. We identified the differences in the DNA methylation status of the extrinsic apoptotic signalling pathway-related genes between AIT and controls and in different iodine levels areas. The results were verified at the mRNA level. The environmental iodine may affect DNA methylation to some extent. [ABSTRACT FROM AUTHOR]

Cucurbitacins constitute a group of cucumber-derived dietary lipids, highly oxidized tetracyclic triterpenoids, with potential medical uses. These compounds are known to interact with a variety of recognized cellular targets to impede the growth of cancer cells. Accumulating evidence has suggested that inhibition of tumor cell growth via induction of apoptosis, cell-cycle arrest, anti-metastasis and anti-angiogenesis are major promising chemo-preventive actions of cucurbitacins. Cucurbitacins may be a potential choice for investigations of synergism with other drugs to reverse cancer cells' treatment resistance. The detailed molecular mechanisms underlying these effects include interactions between cucurbitacins and numerous cellular targets (Bcl-2/Bax, caspases, STAT3, cyclins, NF-κB, COX-2, MMP-9, VEGF/R, etc.) as well as control of a variety of intracellular signal transduction pathways. The current study is focused on the efforts undertaken to find possible molecular targets for cucurbitacins in suppressing diverse malignant processes. The review is distinctive since it presents all potential molecular targets of cucurbitacins in cancer on one common podium. [ABSTRACT FROM AUTHOR]

Persistent lung inflammation is a characteristic of sepsis-induced lung injury. Matrine, the active ingredient from Sophora flavescens , has exhibited anti-inflammatory activities. This study investigated the effects of prophylactic administration of matrine on macrophage polarization, apoptosis, and tissue injury in a cecal ligation and puncture (CLP)–induced murine lung injury model. Mice were randomly allocated into four groups: Sham, CLP, Sham + Matrine, and CLP + Matrine. Lung tissues were collected at 24 h post-CLP. Histopathology and immunofluorescence analysis were performed to evaluate lung injury and macrophage infiltration in the lung, respectively. Caspase-3 activities, TUNEL staining, and anti-apoptotic proteins were examined to assess apoptosis. To determine the mechanism of action of matrine, protein levels of Sirtuin 1 (SIRT1), nuclear factor κB (NF-κB), p53 and the messenger RNA levels of p53-mediated proapoptotic genes were examined to elucidate the associated signaling pathways. Histopathological evaluation showed that matrine prophylaxis attenuated sepsis-induced lung injury. Matrine prophylaxis attenuated sepsis-induced infiltration of the total population of macrophages in the lung. Matrine inhibited M1 macrophage infiltration, but increased M2 macrophage infiltration, thus resulting in a decrease in the proportion of M1 to M2 macrophages in septic lung. Sepsis-induced lung injury was associated with apoptotic cell death as evidenced by increases in caspase-3 activity, TUNEL-positive cells, and decreases in antiapoptotic proteins, all of which were reversed by matrine prophylaxis. Matrine restored sepsis-induced downregulation of SIRT1 and deacetylation of NF-κB p65 subunit and p53, thus inactivating NF-κB pathway and suppressing p53-induced proapoptotic pathway in septic lung. In summary, this study demonstrated that matrine exhibited pro-M2 macrophage polarization and antiapoptotic effects in sepsis-induced lung injury, which might be, at least partly, due to the modulation of SIRT1/NF-κB and SIRT1/p53 pathways. [ABSTRACT FROM AUTHOR]

Radiofrequency electromagnetic fields (RF-EMF) exposure is increasing in various areas of life. In our study, we investigated the effects of 5G (6 GHz, 0.083 W/kg SAR) RF-EMF on the ratio of vitality, apoptotic (the early/late) and necrotic in rat blood cells. In our study, 10 Wistar Albino male rats were used weights range between 250-300g. Before RF-EMF applications, blood samples (2cc) were collected from all rats by cardiac puncture method. These rats were selected as the control groups. The same rats, by placing in the special application cage were exposed to the 6 GHz RF-EMF application for 4 hour/day during 6 weeks. After RF-EMF applications, blood samples (2cc) were recollected from the same rats. These rats were selected as the radiofrequency radiation (RFR) groups. Flow cytometric analysis in which annexin-V kit used, was performed to determine the percentage the ratio of viable, the early/late apoptotic and necrotic cell. The ratio of % viable cells were increased in the RFR group by compared to the control group, the ratio of % cells in the early apoptotic and necrotic decreased and this between the two groups difference was statistically significant (p<0.05). However, there were no statistically meaningful differences between groups by compared to the ratio of % cells in the late apoptotic. As a results of 6 GHz RF-EMF, had significant effects on vitality, apoptotic and necrotic in blood cells. while it supported to the ratio of vitality, were inhibited the ratio of apoptotic and necrotic. [ABSTRACT FROM AUTHOR]

Cancer is being considered as a serious threat to human health globally due to limited availability and efficacy of therapeutics. In addition, existing chemotherapeutic drugs possess a diverse range of toxic side effects. Therefore, more research is welcomed to investigate the chemo-preventive action of plant-based metabolites. Ampelopsin (dihydromyricetin) is one among the biologically active plant-based chemicals with promising anti-cancer actions. It modulates the expression of various cellular molecules that are involved in cancer progressions. For instance, ampelopsin enhances the expression of apoptosis inducing proteins. It regulates the expression of angiogenic and metastatic proteins to inhibit tumor growth. Expression of inflammatory markers has also been found to be suppressed by ampelopsin in cancer cells. The present review article describes various anti-tumor cellular targets of ampelopsin at a single podium which will help the researchers to understand mechanistic insight of this phytochemical.

The term apoptosis, as a way of programmed cell death, was coined a half century ago and since its discovery the process has been extensively investigated. The anatomy and physiology of the head are complex and thus apoptosis has mostly been followed in separate structures, tissues or cell types. This review aims to provide a comprehensive overview of recent knowledge concerning apoptosis-related molecules involved in the development of structures of head with a particular focus on caspases, cysteine proteases having a key position in apoptotic pathways. Since many classical apoptosis-related molecules, including caspases, are emerging in several non-apoptotic processes, these were also considered. The largest organ of the head region is the brain and its development has been extensively investigated, including the roles of apoptosis and related molecules. Neurogenesis research also includes sensory organs such as the eye and ear, efferent nervous system and associated muscles and glands. Caspases have been also associated with normal function of the skin and hair follicles. Regarding mineralised tissues within craniofacial morphogenesis, apoptosis in bones has been of interest along with palate fusion and tooth development. Finally, the role of apoptosis and caspases in angiogenesis, necessary for any tissue/organ development and maintenance/homeostasis, are discussed. Additionally, this review points to abnormalities of development resulting from improper expression/activation of apoptosis-related molecules.

Background: Oral cancer, one of the most common cancers, has unimproved 5-years survival rate in the last 30 years and the chemo/radiotherapy-associated morbidity. Therefore, intervention strategies that evade harmful side effects of the conventional treatment modalities are of need. Herbal therapy as a complementary preventive/therapeutic modality has gained attention. Curcumin is one of the herbal compounds possessing unique anticancer activity and luminescent optical properties. However, its low water solubility limits its efficacy. In contrast, curcumin at the nanoscale shows altered physical properties with enhancing bioavailability. Methods: The current study evaluated the impact of nanocurcumin as an anti-oral cancer herbal remedy, comparing its efficacy against the native curcumin complement and conventional chemotherapeutic. An optimized polymeric-stabilized nanocurcumin was synthesized using the solvent-antisolvent precipitation technique. After assuring the solubility and biocompatibility of nanocurcumin, we determined its cytotoxic dose in treating the squamous cell carcinoma cell line. We then evaluated the anti-tumorigenic activity of the nano-herb in inhibiting wound closure and the cytological alterations of the treated cancer cells. Furthermore, the cellular uptake of the nanocurcumin was assessed depending on its autofluorescence. Results: The hydrophilic optimized nanocurcumin has a potent cancerous cytotoxicity at a lower dose (60.8 µg/mL) than the native curcumin particles (212.4 µg/mL) that precipitated on high doses hindering their cellular uptake. Moreover, the nanocurcumin showed differential targeting of the cancer cells over the normal fibroblasts with a selectivity index of 4.5. With the confocal microscopy, the luminescent nanoparticles showed gradual nuclear and cytoplasmic uptake with apparent apoptotic cell death, over the fluorescent doxorubicin with its necrotic effect. Furthermore, the nanocurcumin superiorly inhibited the migration of cancer cells by -25%. Conclusions: The bioavailable nanocurcumin has better apoptotic cytotoxicity. Moreover, its superior luminescence promotes the theranostic potentialities of the nano-herb combating oral cancer. [ABSTRACT FROM AUTHOR]

Moringa oleifera (MO) has been an important plant for food and traditional medicine in Asian countries, including Indonesia. The leaves of these plants are reported to be rich in antioxidants, vitamins, and micronutrients and have been proven to have nootropic properties. Therefore, we investigated whether MO could provide protective effects on SH-SY5Y neuroblastoma cells exposed to H 2 O 2 . In this study, we observed cotreating water-extracted MO leaves on the inhibition of reactive oxygen species (ROS). We found that this treatment enhanced the activities of glutathione peroxidase, catalase, and superoxide dismutase. In addition, it suppressed the mRNA expression levels of apoptotic gene-related genes, specifically Bcl-2 associated protein X (BAX) and caspase 3. Furthermore, it promoted neuroplasticity by increasing the brain-derived neurotropic factor (BDNF) mRNA expression in SH-SY5Y cells. The protein expression of phosphorylated-Akt and phosphorylated-CREB, essential genes in neuroplasticity, was also increased in cells treated with H 2 O 2 and MO. Therefore, the neuroprotective effects of MO against oxidative stress are attributed to its antioxidant and antiapoptotic properties, as well as its ability to modify the neuronal signaling pathway., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Agian Jeffilano Barinda et al.)

Background: Prostate cancer (Pca) is a deadly disease prevalent among men, and it accounts for about 7-8 % of mortality globally. Synthetic drugs have proved effective but have limitations and severe side effects. There is, therefore, a need to discover a less expensive, natural therapeutic agent with no side effects in treating the ailment., Aim: The study aims to investigate the anti-prostate cancer activity of extracts of Indigofera macrophylla ( I. macrophylla ) at the physiological and molecular levels in experimental animals., Method: Polyphenol-rich extract of I. macrophylla was subjected to HPLC analysis to identify the plant's phytochemical constituent. Adult Wistar rats were orally administered 2mls of 50, 100 and 200 PPM of the cacodylic acid solution for 28 days to induce prostate cancer, while treatment was carried out by orally administering extract of I. macrophylla at doses of 50, 100 and 200 mg/kg for up to 28 days. The anti-inflammatory and apoptotic properties of the extract in experimental animals were investigated by the expression levels of various genetic biomarkers such as Bax-2, TNF-α, IL-6, COX2, IL-1β, β-Catenin, APC, Bcl2, CEA, Caspase 3 and β-Catenin using reverse transcriptase polymerase chain reaction (RT-PCR)., Result: HPLC analysis shows that I. macrophylla has 21 bioactive components which are categorized into seven groups: flavonoid, terpenes, phenols, isoflavonoid, phytosterols, quinone and glycosides. Administration of the drug shows inconsistencies in the mean body weights of the experimental animals. Further investigation revealed that I. macrophylla increased TNF-α upregulation and expression, significantly downregulated IL-1β, significantly decreased IL-6 expression, ameliorated COX2 expression, downregulated β-catenin expression and significantly reduced the expression of the APC gene. These results show that the drug activity modulates the investigated inflammatory and apoptotic genes in the prostate gland of PCa-induced rats, thus demonstrating its anti-PCa potential., Conclusion: The results of this study suggest the potential of a novel treatment protocol of I. macrophylla plant extract to improve therapeutic outcomes for patients with aggressive PCa, which reportedly claims hundreds of thousands of lives yearly., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The goal of this study was to determine the genotoxic potential of a hydroalcoholic extract of Nargis flowers (Narcissus Tazetta L.). The genotoxicity potential of standardized hydroalcoholic extract of Narcissus Tazetta L at different concentrations was assessed using human breast cancer cells applying the MTT test for cell cytotoxicity. In control cells, Nargis flowers extract did not totally break DNA, however, flowers-treated cells showed high amounts of damage in a dose-dependent way. According to the findings, the crude hydroalcoholic extract of Narcissus Tazetta (Nargis flowers) had a potent inhibitory effect on human breast carcinoma cancer cell proliferation, which was mediated by its pro-apoptotic antiproliferative activity.

Thymoquinone nanoparticles (TQNPs) are broadly utilized in numerous pharmaceutical applications. In the present study, we tested the effects of TQNP supplementation on sperm quality and kinematics, acrosome exocytosis, oxidative biomarkers, apoptosis-like and morphological changes of frozen–thawed buffalo sperm, as well as the fertilizing capacity. Semen was collected from buffalo bulls, diluted (1:10; semen/extender), and divided into five aliquots comprising various concentrations of TQNP 0 (CON), 12.5 (TQNP12.5), 25 (TQNP25), 37.5 (TQNP37.5), and 50 (TQNP50) µg/mL, and then cryopreserved and stored in liquid nitrogen (−196 °C). The results revealed that TQNPs (25 to 50 µg/mL) provided the most optimal results in terms of membrane integrity (p < 0.001) and progressive motility (p < 0.01). In contrast, TQNP50 resulted in a greater post-thawed sperm viability (p = 0.02) compared with other groups. The addition of TQNPs to the extender had no discernible effects on sperm morphology measures. Sperm kinematic motion was significantly improved in the TQNP50 group compared to the control group (p < 0.01). TQNPs effectively reduced the content of H2O2 and MDA levels and improved the total antioxidant capacity of post-thawed extended semen (p < 0.01). The addition of TQNP significantly increased the number of intact acrosomes (p < 0.0001) and decreased the number of exocytosed acrosomes (p < 0.0001). A significant reduction in apoptosis-like changes was observed in TQNP groups. The non-return rates of buffalo cows inseminated with TQNP50-treated spermatozoa were higher than those in the control group (p < 0.05; 88% vs. 72%). These findings suggested that the freezing extender supplemented with TQNPs could effectively enhance the cryotolerance and fertility of buffalo sperm.