Natural products and derivatives for breast cancer treatment: From drug discovery to molecular mechanism.

BACKGROUND: Breast cancer stands as the most common malignancy among women globally and a leading cause of cancer-related mortality. Conventional treatments, such as surgery, hormone therapy, radiotherapy, chemotherapy, and small-molecule targeted therapy, often fall short of addressing the complexity and heterogeneity of certain breast cancer subtypes, leading to drug resistance and metastatic progression. Thus, the search for novel therapeutic targets and agents is imperative. Given their low toxicity and abundant variety, natural products and their derivatives are increasingly considered valuable sources for small-molecule anticancer drugs. PURPOSE: This review aims to elucidate the pharmacological impacts and underlying mechanisms of active compounds found in select natural products and their derivatives, primarily focusing on breast cancer treatment. It intends to underscore the potential of these substances in combating breast cancer and guide future research directions for the development of natural product-based therapeutics. METHODS: We conducted comprehensive searches in electronic databases such as PubMed, Web of Science, and Scopus until October 2023, using keywords such as 'breast cancer', 'natural products', 'derivatives', 'mechanism', 'signaling pathways', and various keyword combinations. RESULTS: The review presents a spectrum of phytochemicals, including but not limited to flavonoids, polyphenols, and alkaloids, and examines their actions in various animal and cellular models of breast cancer. The anticancer effects of these natural products and derivatives are manifested through diverse mechanisms, including induction of cell death via apoptosis and autophagy, and suppression of tumor angiogenesis. CONCLUSION: An increasing array of natural products and their derivatives are proving effective against breast cancer. Future therapeutic strategies can benefit from strategic enhancement of the anticancer properties of natural compounds, optimization for targeted action, improved bioavailability, and minimized side effects. The forthcoming research on natural products should prioritize these facets to maximize their therapeutic potential.

Dietary intakes of vitamin D promote growth performance and disease resistance in juvenile grass carp (Ctenopharyngodon idella).

Vitamin D3 (VD3) is an essential nutrient for fish and participates in a variety of physiological activities. Notably, both insufficient and excessive supplementation of VD3 severely impede fish growth, and the requirements of VD3 for fish vary considerably in different species and growth periods. The present study aimed to evaluate the appropriate requirements of VD3 for juvenile grass carp (Ctenopharyngodon idella) according to growth performance and disease prevention capacity. In this study, diets containing six supplemental levels of VD3 (0, 300, 600, 1200, 2400, and 4800 IU/kg diet) were formulated to investigate the effect(s) of VD3 on the growth performance, antioxidant enzyme activities, and antimicrobial ability in juvenile grass carp. Compared with the VD3 deficiency group (0 IU/kg), the supplementation of 300-2400 IU/kg VD3 significantly enhanced growth performance and increased antioxidant enzyme activities in the fish liver. Moreover, dietary supplementation of VD3 significantly improved the intestinal health by manipulating the composition of intestinal microbiota in juvenile grass carp. In agreement with this notion, the mortality of juvenile grass carp fed with dietary VD3 was much lower than that in VD3 deficient group upon infection with Aeromonas hydrophila. Meanwhile, dietary supplementation of 300-2400 IU/kg VD3 reduced bacterial load in the spleen and head kidney of the infected fish, and 1200 IU/kg VD3 supplementation could decrease enteritis morbidity and increase lysozyme activities in the intestine. These findings strengthened the essential role of dietary VD3 in managing fish growth and antimicrobial capacity. Additionally, based on weight gain ratio and lysozyme activities, the appropriate VD3 requirements for juvenile grass carp were estimated to be 1994.80 and 2321.80 IU/kg diet, respectively.

Electroacupuncture Attenuates Ventilator-Induced Lung Injury by Modulating the Nrf2/HO-1 Pathway.

INTRODUCTION: Ventilator-induced lung injury (VILI) is the most common complication associated with mechanical ventilation. Electroacupuncture (EA) has shown potent anti-inflammatory effects. This study aimed to investigate the effects of EA on VILI and explore the underlying mechanisms. METHODS: Male C57BL/6 mice were subjected to high tidal volume ventilation to induce VILI. Prior to mechanical ventilation, mice received treatment with EA, nonacupoint EA, or EA combined with zinc protoporphyrin. RESULTS: EA treatment significantly improved oxygenation, as indicated by increased PaO2 levels in VILI mice. Moreover, EA reduced lung injury score, lung wet/dry weight ratio, and protein concentration in bronchoalveolar lavage fluid. EA also decreased the expression of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, IL-18, chemokine keratinocyte chemoattractant, macrophage inflammatory protein 2, and malondialdehyde. Furthermore, EA increased the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in VILI mice. At the molecular level, EA upregulated the expression of Nrf2 (nucleus) and heme oxygenase -1, while down-regulating the expression of p-NF-κB p65, NLR Family Pyrin Domain Containing 3, Cleaved Caspase-1, and ASC in VILI mice. Notably, the effects of EA were reversed by zinc protoporphyrin treatment, nonacupoint EA did not affect the aforementioned indicators of VILI. CONCLUSIONS: EA alleviates VILI by inhibiting the NLR Family Pyrin Domain Containing three inflammasome through activation of the Nrf2/HO-1 pathway.

Effect of traditional Chinese medicine combined group psychotherapy on psychological distress management and gut micro-biome regulation for colorectal cancer survivors: a single-arm phase I clinical trial.

OBJECTIVE: To evaluate the efficacy and feasibility of utilizing Traditional Chinese Medicine (TCM) combined group psychotherapy intervention on psychological distress management and gut micro-biome regulation for colorectal (CRC) survivors. METHODS: A single-arm phase I clinical trial was conducted between December 2020 and December 2021 in Xiyuan Hospital and Beijing Cancer Hospital in China. Inclusion criteria included stage I-III CRC survivors after radical surgery with age between 18 and 75. The intervention was a 6-week online TCM combined group psychotherapy intervention including 90-min communication, TCM lifestyle coaching, self-acupressure guidance, and mindfulness practice led by TCM oncologist and psychiatrist each week. Outcomes were measured by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Fear of Cancer Recurrence Inventor (FCRI), and Quality of Life Questionnaire (QLQ-C30). Fecal samples before and after intervention were collected for 16Sr RNA analysis. RESULTS: We recruited 40 CRC survivors and 38 of them finally completed all interventions with average age of 58±13 years' old. Paired t-test showed that SAS at week 2(35.4±5.8), week 4 (37.9±10.5) and week 6 (31.3±6.4) during the intervention was significantly lower than baseline (42.1±8.3, p<0.05 respectively). SDS score also declined substantially from baseline (38.8±10.7) to week 2 (28.3±8.8, p<0.001) and week 6 (25.4±7.7, p<0.001). FCRI decreased from 19.4±7.2 at baseline to 17.5±7.1 at week 4 (p=0.038) and 16.3±5.8 at week 6 (p=0.008). Although changes of QLQ-C30 were not statistically prominent, symptom burden of insomnia and fatigue significantly alleviated. The abundances of gut microbiota Intestinibacter, Terrisporobacter, Coprobacter, and Gordonibacter were all significantly elevated after intervention. CONCLUSIONS: TCM combined group psychotherapy intervention is feasible and effective to reduce CRC survivors' psychological distress and modulate certain gut bacteria which might be associated with brain-gut axis effect. It is necessary to carry out with phase II randomized controlled clinical trial.

The effect of mindfulness on social media addiction among Chinese college students: A serial mediation model.

Introduction: The COVID-19 pandemic has exacerbated social media addiction (SMA), making it urgent to find effective interventions for social media addiction. Evidence has shown that mindfulness might be an effective intervention for social media addiction. However, psychological mechanisms by which mindfulness reduce social media use remain unclear. Here, we further addressed this issue to examine whether attentional control and fear of missing out (FOMO) mediate the relationship between mindfulness and SMA. Methods: We recruited 446 college students from two universities in China and analyzed the data. Results: The results suggest that there are mediation effects of attentional control and FOMO between mindfulness and SMA through 3 paths: path 1, mindfulness → attention control → SMA (-0.04); path 2, mindfulness → FOMO → SMA (-0.22); and path 3, mindfulness → attention control → FOMO → SMA (-0.05). Discussion: Therefore, mindfulness-based interventions may be an effective way to alleviate social media addiction, especially mindfulness-based interventions targeting FOMO. At the end of the article, we also discussed the limitations of this study.

Morphological differences between anemophilous and entomophilous pollen.

In order to provide a palynological guide for the identification of insect-carrying pollen grains, we studied the pollen grains of 10 anemophilous species and 10 entomophilous species in the Beijing urban area using light and scanning electron microscopies. We found that anemophilous pollen grains are small, spheroidal, or oblate spheroidal, while entomophilous pollen grains are medium and oblate. Comparison of the exine thickness and surface ornamentation showed that anemophilous pollen grains have significantly thinner exine and smoother surface ornamentation than entomophilous pollen grains. The results also revealed pollen characteristics adaptive to different pollination types. Overall, our study indicated that pollen morphology might be helpful for preliminary identification of anemophilous and entomophilous pollen.

Taxonomic importance of pollen morphology in Veratrum L. (Melanthiaceae) using microscopic techniques.

Previous studies reported that intrageneric relationships of genus Veratrum of family Melanthiaceae are controversial and hard to delimit. Therefore, we observed the pollen morphological features of six species in the genus Veratrum in detail using both light microscopy and scanning electron microscopy and investigated their significance for Veratrum taxonomy. Among them, five were studied for the first time. The results demonstrated that pollen grains of Veratrum are medium in size with P/E being 0.31-0.60. Three types of shape in polar view have been observed elliptic, long-elliptic, or wide-elliptic with blunt or rounded at both ends. Two types of width of colpus reported narrow or wide, two types of depth of colpus reported deep or flat, and two types of length of colpus reported extend almost or do not extend to the ends, whereas two types of colpus membranes reported absent or obvious. One type of surface ornamentation was noted as reticulate. These results support species Veratrum album and Veratrum lobelianum as well as Veratrum grandiflorum and Veratrum oxysepalum as two independent species, respectively, rather than classifying Veratrum into two sections. Overall, we demonstrated that the ratio of polar axis length to equatorial axial length, pollen characteristics at the polar view, the colpus morphology, and the surface ornamentation of pollen grains of genus Veratrum have important systematic significance in identification and delimitation of species.

Pollen morphology of Chinese Pseudostellaria (Caryophyllaceae) and its systematic significance.

Using light and scanning electron microscopy, we studied the pollen morphology of six species (one of which are endemic) of Chinese Pseudostellaria. All species were studied for the first time. Results of this study indicated that pollen grains of Pseudostellaria are spheroidal or spheroidal-polyhedral in shape and small or medium in size and pantoporate. Each pollen grain has 12-16 round pores. These pores are apart from each other by 5.77-7.73 µm and each has 7-13 granules in the operculum region. These features have important taxonomic significance. In addition, their pollen grains have thin exine with microechinate-punctate-perforate surface ornamentation. Pollen features do not support the traditional infrageneric classification of Pseudostellaria into two sections, but support that Pseudostellaria is closely related to other species of the Odontostemma clade.

Pollen morphology of Aletris L. (Nartheciaceae) and its systematic significance.

In this paper, we studied pollen morphologies of seven species in genus Aletris in detail by light microscopy and scanning electron microscopy. Of these, six species were reported for the first time. The palynological characteristics do not support the infrageneric classification into two clades. The results indicated that pollen grains of Aletris are small or medium with the P/E ratio of 0.36-0.59. They are elliptic or long-elliptic in the polar view with blunt, round or acute ends and bilateral symmetric with a monosulcate, narrow or wide, deep colpus that has length extending to the ends of pollen grains, obvious or absent colpus membranes. The pollen ornamentation is gemmate, perforated, or reticulate. The sexine is slightly or quite thicker than the nexine.

[Preliminary Studies on the Relationship Between Meiosis of Pollen Mother Cells and Pollen Abortion of Aloe arboresense Mill.].

The main reason for pollen abortion in Aloe arboresens Mill. was studied through the observation of meiosis and the microspore development of its pollen mother cells(PMCs). There are 14 chromosomes in the PMC of Aloe arboresens Mill., containing four pairs of long chromosomes and three pairs of short ones, and this karyotype belongs to dichotocarpism. Abnormalities observed were fallen into four categories:(1) Univalents, they were caused by failure in pairing, asynapsis and precocious cancellation of terminal chiasma. Oriented univalent pair was distributed at two poles normally in anaphase, while non-oriented univalent pair only at one pole. Another factor leading to univalents was that chromosomes were paired but without substantial exchange. (2) Multivalents. They might be produced by translocation heterozygote.(3) Chromosome bridges. There were three kinds of bridges in anaphase I and anaphase II: single and double chromosome bridge as well as "diagonal bridge".(4) A few cells were found with lagged chromosomes, micronuclei and unbalanced segregation of the chromosomes. In the later stages of meiosis, well-spread chromosomal configurations were rare because of the extremely sticky nature of the chromosome. The number and ratio of abnormalities were analysed and the relationship between abnormalities and pollen sterility were discussed. It is concluded that the sticky nature of the chromosome is the main reason for abnormal meiosis of Aloe arboresens Mill.PMC and pollen sterility. More than 90% of matured pollen grains were sterile.