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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]

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]

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.

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]

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.

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.

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]

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.

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.

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.

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.

Seahorse (Hippocampus spp) is marine fish and have pharmacological activity, such as an antiinflammatory, antioxidative, antifatigue and improve the fertility. Depot medroxyprogesterone acetate (DMPA) is a contraception drug for male and affect the endocrine system by inhibiting pituitary gonadotropin with reduce testosterone levels in 12 weeks. There are limited studies reported the effects seahorse extract (SE) on Caspase-3 and TUNEL assay in rats induced by DMPA. Thirty Sprague-Dawley (SD) male rats that were induced by 1.25mg/kgbw DMPA in 0 and 12 weeks. The animals were randomly into five groups, following: aquadest (G1), CMC 1% (G2), SE dose of 150 mg/kgbw (G3), SE dose of 225 mg/kgbw (G4), SE dose of 300 mg/kgbw (G5). The rats were gavage every day from seven until week eighteen. On the last week, we taken the right and left testis to observed the apoptotic on Caspase-3 and TUNEL assay. Apoptotic marker was observed through immunohistochemistry from testicular tissue and analysed with plugin ImageJ IHC profiler, which is H-score as the results. Data were analysed using One-Way ANOVA and Bonferroni's post hoc tests. The SE decrease the Caspase-3 and TUNEL assay expression in rats induced by DMPA until eighteen weeks, with dose 150 mg/kgbw given the significant difference with p=0.028; <0.05 and p=0.000; <0.01. These results suggest that SE decreased germ cells apoptotic in DMPA induced rats. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the most common cause of death in the world. One of the major causes of cardiac death is excessive apoptosis. However, multiple pathways through moderate exercise can reduce myocardial apoptosis. After moderate exercise, the expression of anti-apoptotic proteins such as IGF-1, IGF-1R, p-PI3K, p-Akt, ERK-1/2, SIRT3, PGC-1α, and Bcl-2 increases in the heart. While apoptotic proteins such as PTEN, PHLPP-1, GSK-3, JNK, P38MAPK, and FOXO are reduced in the heart. Exercise-induced mechanical stress activates the β and α5 integrins and subsequently, focal adhesion kinase phosphorylation activates the Akt/mTORC1 and ERK-1/2 pathways, leading to an anti-apoptotic response. One of the reasons for the decrease in exercise-induced apoptosis is the decrease in Fas-ligand protein, Fas-death receptor, TNF-α receptor, Fas-associated death domain (FADD), caspase-8, and caspase-3. In addition, after exercise mitochondrial-dependent apoptotic factors such as Bid, t-Bid, Bad, p-Bad, Bak, cytochrome c, and caspase-9 are reduced. These changes lead to a reduction in oxidative damage, a reduction in infarct size, a reduction in cardiac apoptosis, and an increase in myocardial function. After exercising in the heart, the levels of RhoA, ROCK1, Rac1, and ROCK2 decrease, while the levels of PKCε, PKCδ, and PKCɑ are activated to regulate calcium and prevent mPTP perforation. Exercise has an anti-apoptotic effect on heart failure by increasing the PKA-Akt-eNOS and FSTL1-USP10-Notch1 pathways, reducing the negative effects of CaMKIIδ, and increasing the calcineurin/NFAT pathway. Exercise plays a protective role in the heart by increasing HSP20, HSP27, HSP40, HSP70, HSP72, and HSP90 along with increasing JAK2 and STAT3 phosphorylation. However, research on exercise and factors such as Pim-1, Notch, and FAK in cardiac apoptosis is scarce, so further research is needed. Future research is recommended to discover more anti-apoptotic pathways. It is also recommended to study the synergistic effect of exercise with gene therapy, dietary supplements, and cell therapy for future research.

Abstract Background T-2 toxin is a mycotoxin produced by Fusarium species that is highly toxic to animals. Recent studies have indicated that Selenomethionine (SeMet) have protective effect against mycotoxins-induced toxicity. The aim of the present study was to investigate the protective effect of SeMet on T-2-toxin-induced liver injury in rabbit and explore its molecular mechanism. Fifty rabbits (30 d, 0.5 ± 0.1 kg) were randomly divided into 5 groups: control group, T-2 toxin group, low, medium and high dose SeMet treatment group. The SeMet-treated group was orally pretreated with SeMet (containing selenium 0.2 mg/kg, 0.4 mg/kg and 0.6 mg/kg) for 21 days. On the 17th day, T-2 toxin group and SeMet-treated group were orally administered with T-2 toxin (0.4 mg/kg body weight) for 5 consecutive days. Results The results showed that low-dose SeMet significantly improved T-2 toxin-induced liver injury. We found that low-dose SeMet can reduce the level of oxidative stress and the number of hepatocyte apoptosis. Moreover, the levels of Bax, caspase-3 and caspase-9 were significantly reduced and the levels of Bcl-2 were increased. Conclusions Therefore, we confirmed that low-dose SeMet may protect rabbit hepatocytes from T-2 toxin by inhibiting the mitochondrial-caspase apoptosis pathway.

Abstract Background Cancer is currently the leading cause of death globally and the number of deaths from cancer is on the rise daily. Medicinal plants have been in continuous use over the years for the management of cancer, particularly, in most developing countries of the world including Nigeria. The use of synthetic drugs for the treatment of cancer is often accompanied by toxic side effects. Thus, the alternative use of readily available and inexpensive medicinal plants is the panacea to the toxic side effects associated with synthetic drugs. Main body The present review summarized the anticancer activity of 51 medicinal plants that are widespread in all regions of Nigeria. Furthermore, the proposed anticancer pharmacological actions as well as the anticancer bioactive compounds, the type of cancer cell inhibited, the plant parts responsible for the anticancer activity, and the nature of the extracts used for the studies were discussed in this review. The 51 Nigerian medicinal plants were reported to exhibit anticancer activities of the prostate, cervices, lung, skin, colon, esophagus, blood, ovary, central nervous system/brain, breast, stomach, pancreas, larynx, and kidney. The major classes of bioactive compounds indicated to be responsible for the anticancer activity include the polyphenols, flavonoids, alkaloids, saponins, triterpenes, tannins, and quinones. The major anticancer pharmacological actions of these bioactive compounds were antiproliferative, cytotoxic, cytostatic, antimetastatic, apoptotic, and antioxidative as well as provoked cell cycle arrest, inhibition of angiogenesis and reduction of cancer cell viability. Conclusion The Nigerian medicinal plants can be harnessed to provide for readily available and inexpensive anticancer drugs in the future because the plants reported in this review showed promising anticancer activity.

Colorectal cancer usually refers to the occurrence of the appendix, rectum or colon and other parts of the malignant tumor in the large intestine mucosa and glands, is also one of the most common malignant tumors in human. In recent years, studies have shown that chronic inflammation is the ''initiator'' of cancer. Inflammation plays a causal role in the early formation of tumors by regulating the initiation and promotion of tumor genesis and development through a series of inflammatory cytokines. Inflammation plays a causal role in the early formation of tumors by regulating the initiation and promotion of tumor genesis and development through a series of inflammatory cytokines. The latter part of this review describes the role of several important inflammatory factors: tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and transforming growth factor-β (TGF-β) in colorectal cancer. In normal mucosa, inflammatory factors play an important role in the immune response of the body. However, when a large number of inflammatory factors accumulate, they will cause pathological damage to the body, trigger inflammation and even deteriorate into cancer. Serum levels of most inflammatory factors were low in healthy controls, but were elevated in colorectal cancer patients. Here, we review the relationship between apoptosis, inflammation and cancer, and analyze the difference in the expression of inflammatory proteins in colorectal cancer and its adjacent mucosa.

MiR-128 is highly expressed in the central nervous system and may regulate the directional differentiation of bone marrow stromal stem cells into nerve cells. However, its role and mechanism in sevoflurane-induced progressive neurotoxicity in rats are rarely reported. Therefore, this study aims to explore the protection of miR-128-3p on sevoflurane-induced neurotoxicity. Hippocampal neurons were isolated and sevoflurane was used to treat the cells. Cell counting kit-8 (CCK-8) was used to detect cell viability. Immunofluorescence was used to detect enrichment of GFAP or ßIII tubulin to identify nerve cells. Dual luciferase assay was used to identify the targeted binding relationship between miR-128-3p and NOVA1. The effect of miR-128-3p and sevoflurane on cells regarding apoptosis was detected by flow cytometry. The expression of apoptosis-related protein and oxidative stress-related proteins were detected by western blot. Enzyme-linked immuno-sorbent assay (ELISA) was used to measure inflammatory cytokine levels. Hippocampal neurons' cell viability was significantly decreased by treatment with sevoflurane. MiR-128-3p was down-regulated after sevoflurane treatment in cells. Overexpressed miR-128-3p partially reversed the role of sevoflurane treatment in triggering cell apoptosis, enhancing the expression of Bax and cleaved caspase-3 and inhibiting Bcl-2 expression obviously. Overexpressed miR-128-3p partially reversed the role of sevoflurane treatment in promoting the expression of NOX1and NOX4, and inflammatory cytokine levels by targeting with NOVA1. MiR-128-3p might be a potential therapeutic target for the prevention or treatment of sevoflurane-induced neurotoxicity by targeting with NOVA1. [ABSTRACT FROM AUTHOR]

The harm of air pollution to public health has become a research hotspot, especially atmospheric fine-particulate matter (PM2.5). In recent years, epidemiological investigations have confirmed that PM2.5 is closely related to chronic kidney disease and membranous nephropathy Basic research has demonstrated that PM2.5 has an impact on the normal function of the kidneys through accumulation in the kidney, endothelial dysfunction, abnormal renin-angiotensin system, and immune complex deposition. Moreover, the mechanism of PM2.5 damage to the kidney involves inflammation, oxidative stress, apoptosis, DNA damage, and autophagy. In this review, we summarized the latest developments in the effects of PM2.5 on kidney disease in human and animal studies, so as to provide new ideas for the prevention and treatment of kidney disease. [ABSTRACT FROM AUTHOR]

Objective: Paclitaxel (PAC) is a chemotherapy drug and has an active role in the treatment of lung, breast, and ovarian cancers; however, its use causes increased levels of free radicals, leading to severe and irreversible organ damage. Thymus vulgaris is a species of flowering plant that contains various antioxidant chemical compounds. This study aimed to investigate the effect of T. vulgaris on PAC-induced oxidative damage in mice testis and sperm parameters. Methods: In this study, 40 BALB/c mice were divided into five groups: normal control (NC); positive control (20 mg/kg of PAC); and three treatment groups (4.5, 9, and 18 mg/kg doses of T. vulgaris extract + 20 mg/kg PAC). Treatments were administered intraperitoneally daily for 50 days. Finally, the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured using immunoassay method. Testicular stereological features and sperm parameters were also calculated. Antioxidant parameters were measured using nitrite oxide (NO) and perioxidation levels and ferric-reducing ability of plasma assay. The expressions of p53, caspase-3, Bax, and Bcl-2 were measured through real-time quantitative polymerase chain reaction. Results: T. vulgaris + PAC treatments at all doses significantly increased all parameters in NC and three treatment groups compared with the positive control group (20 mg/kg of PAC) (P < 0.05), except the LH, FSH, and NO levels, which were decreased. Further, significantly downregulated levels of p53, caspase-3, and Bax genes and? upregulated levels of Bcl-2 gene expression were noted in NC and three treatment groups in comparison with the positive control group (P < 0.05). Conclusions: T. vulgaris administration attenuates the toxic effects of PAC on male reproductive parameters.

Lead (Pb), as a toxic heavy metal pollutant, has been paid much attention. Pb is often discharged into the environment through the soot, wastewater and waste residue in industrial production, which poses a great threat to animal health. Selenium (Se) is a trace element known to antagonize the toxicity caused by heavy metals. However, the interaction between Se and Pb in chicken kidney and its specific biological mechanism are still unclear. So, we constructed chicken models of Pb exposure and Pb, Se co-exposure. Therefore, we used western blot and qRT-PCR to detect the expression of related genes. The results showed that Pb activated the MAPK signaling pathway by up-regulating the expression of MARK pathway genes to induce the expression of pro-apoptotic genes and necroptosis-related genes. Se can regulate the MARK signaling pathway and attenuated the expression of MAPK pathway genes altered by Pb to reduce apoptosis and necroptosis of chicken kidney cells. Our study gives new ideas for the specific mechanism of Pb nephrotoxicity and provides a reference for comparative medicine and clinical medication.

Non-small cell lung cancer (NSCLC) accounts for 80–85% of all lung cancers, which has the highest cancer-related mortality worldwide. Regardless of the therapeutic effects of chemotherapy or targeted therapy, drug resistance will occur after 1 year. Heat shock proteins (HSPs) are a class of molecular chaperones participated in protein stability and multiple intracellular signaling pathways. It has been widely reported that HSPs family is over expressed in non-small cell lung cancer, and these molecules are also associated with protein stability and multiple intracellular signaling pathways. The effect of chemotherapy drugs or targeted drugs on cancer cells is usually to induce apoptosis. It is necessary to explore the interaction between heat shock protein family and apoptosis pathway in NSCLC. Here we provide a brief review of how HSPs affect the apoptotic pathway in NSCLC.

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.