Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Citrus, which has been consumed internationally for a long time, is widely used as a health food. Citrus and its active components exert significant effects on oxidative stress and lipid metabolism, which are closely associated with female reproductive health. Studies suggest that citrus-derived compounds may alleviate oxidative stress by activating signaling pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Sirtuin 1 (SIRT1), and improve lipid metabolism through the activation of pathways such as peroxisome proliferator-activated receptor α (PPARα). This review focuses on the effects of Citrus on oxidative stress and lipid metabolism, aiming to provide new insights for promoting female reproductive health; however, further work is needed to elucidate the mechanisms involved and validate the therapeutic potential of Citrus's bioactive components in clinical settings.
Citrus/chemistry* ; Oxidative Stress/drug effects* ; Female ; Humans ; Lipid Metabolism/drug effects* ; Reproductive Health ; Animals ; Sirtuin 1/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Signal Transduction/drug effects* ; PPAR alpha/metabolism*

OBJECTIVE: To observe the clinical efficacy of different acupuncture methods in the treatment of ankylosing spondylitis (AS) at different stages. METHODS: Thirty-two patients with AS were treated with acupuncture at ashi points (tendon focus), triple acupuncture method was used in the acute phase, accompanied needling method was used in the remission phase, once a day, 5 times a week for 4 weeks. The Bath ankylosing spondylitis disease activity index (BASDAI) score, Bath ankylosing spondylitis functional index (BASFI) score and TCM symptom grade quantitative standard score before and after treatment were observed, and the efficacy was evaluated. RESULTS: After treatment, the BASDAI score, BASFI score and TCM symptom grade quantitative standard score were reduced compared with those before treatment (P<0.01), the effective rate was 96.9% (31/32). CONCLUSION Different acupuncture methods in the treatment of AS at different stages could improve signs and symptoms, such as pain, activity limitation and morning stiffness.
Humans ; Spondylitis, Ankylosing/physiopathology* ; Acupuncture Therapy/methods* ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; Acupuncture Points ; Treatment Outcome

Insomnia is a prevalent disorder characterized by difficulties in falling asleep or maintaining sleep.Chronic insomnia can severely impair physical and mental health,as well as quality of life.The traditional Chinese medicine(TCM)theory,"all the eleven zang organs depend on the gallbladder,"is derived from the chapter of Discussion on Six-Plus-Six System and the Manifestations of Organs of Plain Questions.It highlights the pivotal role of the gallbladder in maintaining visceral function.The gallbladder governs decision-making and plays a central role in sleep regulation by modulating spleen-stomach transportation and transformation,dispersing qi movement throughout the body,harmonizing yin and yang,and modulating ying and wei systems.Research has demonstrated that bile acids correspond closely with the gallbladder's TCM functions of"governing the earth zang"and"regulating the eleven zang organs,"serving as a crucial material basis for gallbladder physiology.Dysregulation of bile acid metabolism may contribute to insomnia through multiple pathways,including gastrointestinal dysfunction,disruption of gut microbiota balance,induction of neuroinflammation,and circadian rhythm disturbances.This study proposes that bile acid metabolism disorder may constitute a key pathological mechanism linking gallbladder dysfunction—according to TCM theory—to insomnia.Based on clinical experience,novel therapeutic strategies are proposed under the framework of"regulating the gallbladder to tranquilize mind",including the use of gallbladder-related materials,prioritized application of liver-regulating herbs,and implementation of a sleep rhythm reconstruction protocol.

Insomnia is a prevalent disorder characterized by difficulties in falling asleep or maintaining sleep.Chronic insomnia can severely impair physical and mental health,as well as quality of life.The traditional Chinese medicine(TCM)theory,"all the eleven zang organs depend on the gallbladder,"is derived from the chapter of Discussion on Six-Plus-Six System and the Manifestations of Organs of Plain Questions.It highlights the pivotal role of the gallbladder in maintaining visceral function.The gallbladder governs decision-making and plays a central role in sleep regulation by modulating spleen-stomach transportation and transformation,dispersing qi movement throughout the body,harmonizing yin and yang,and modulating ying and wei systems.Research has demonstrated that bile acids correspond closely with the gallbladder's TCM functions of"governing the earth zang"and"regulating the eleven zang organs,"serving as a crucial material basis for gallbladder physiology.Dysregulation of bile acid metabolism may contribute to insomnia through multiple pathways,including gastrointestinal dysfunction,disruption of gut microbiota balance,induction of neuroinflammation,and circadian rhythm disturbances.This study proposes that bile acid metabolism disorder may constitute a key pathological mechanism linking gallbladder dysfunction—according to TCM theory—to insomnia.Based on clinical experience,novel therapeutic strategies are proposed under the framework of"regulating the gallbladder to tranquilize mind",including the use of gallbladder-related materials,prioritized application of liver-regulating herbs,and implementation of a sleep rhythm reconstruction protocol.

Objective::To evaluate the performance of optical genome mapping (OGM) in identifying an inversion located in the short arm of chromosome 8 (8p, 8p23.1), flanked by regions of complex segmental duplication (SD), using the GRCh38 and telomere-to-telomere (T2T) genome references.Methods::We investigated a couple suspected of carrying the 8p23.1 inversion due to a terminal deletion combined with an interstitial duplication of 8p found in their abortus. OGM was performed on both individuals. The data were mapped to the current GRCh38 and the updated T2T genome references, respectively.Results::The 8p23.1 inversion was observed in the female when mapping OGM data to the T2T assembly. In contrast, under the GRCh38 reference, the orientation between the suspected breakpoints within the SD regions could not be distinguished. Additional variants of uncertain significance were also identified in both individuals.Conclusion::Our findings highlight the superiority of the T2T reference in recognizing structural variations involving SD regions. The enhanced SV detection using the T2T reference may contribute to a better understanding of genome instability and human diseases.

Objective::To evaluate the performance of optical genome mapping (OGM) in identifying an inversion located in the short arm of chromosome 8 (8p, 8p23.1), flanked by regions of complex segmental duplication (SD), using the GRCh38 and telomere-to-telomere (T2T) genome references.Methods::We investigated a couple suspected of carrying the 8p23.1 inversion due to a terminal deletion combined with an interstitial duplication of 8p found in their abortus. OGM was performed on both individuals. The data were mapped to the current GRCh38 and the updated T2T genome references, respectively.Results::The 8p23.1 inversion was observed in the female when mapping OGM data to the T2T assembly. In contrast, under the GRCh38 reference, the orientation between the suspected breakpoints within the SD regions could not be distinguished. Additional variants of uncertain significance were also identified in both individuals.Conclusion::Our findings highlight the superiority of the T2T reference in recognizing structural variations involving SD regions. The enhanced SV detection using the T2T reference may contribute to a better understanding of genome instability and human diseases.

Objective:To investigate the correlation between variations in mitochondrial DNA (mtDNA) control region (D-loop) and keloids.Methods:A total of 216 patients with keloids were collected from Department of Dermatology, the First Affiliated Hospital of Kunming Medical University from 2016 to 2019. Total DNA was extracted from peripheral blood samples of all the patients, as well as keloid tissues and perilesional normal skin tissues of 25 patients with keloids. Peripheral blood samples were collected from 299 health checkup examinees without keloids in Health Examination Center, the Affiliated Hospital of Yunnan University, who served as controls. PCR amplification and Sanger sequencing were performed on the mtDNA D-loop region, and mutation sites in each sample were analyzed by comparisons with the revised Cambridge Reference Sequence (rCRS) . Haplogroups were assigned in the 2 groups by using Phylotree-mtDNA tree Build 17. Mutations in the mtDNA D-loop region were compared among keloid tissues, perilesional normal skin tissues and peripheral blood samples. A median-joining network was constructed via network 5.0 software. Binary logistic regression analysis was performed to investigate the correlation between haplogroup frequencies and the occurrence of keloids, and chi-square, t and t′ tests were used to analyze clinical data. Results:Among the 216 patients with keloids, variations in mtDNA D-loop region were classified into 10 haplogroups, including A, B, D, R9, G, M*, M7, M8, M9 and N9, with the haplogroups R9 and M9 showing the highest (21.3%, 46/216) and lowest (0.9%, 2/216) frequencies respectively. The frequencies of haplogroups M7 ( P=0.040, OR=0.248, 95% CI: 0.066 - 0.937) and N9 ( P=0.048, OR=0.191, 95% CI: 0.037-0.986) were significantly lower in the patients with keloids than in the controls. The median-joining network plot showed that the distribution pattern of the haplogroup M7 differed between the patients with keloids and controls. Significantly less number of lesional sites and younger age of onset were observed in the patients with haplogroup M7 compared with those with non-M7 haplogroups ( P=0.000 1, 0.045, respectively) . Conclusion:The haplogroup M7 is correlated with the occurrence of keloids, and may be a potential protective factor for keloid formation.

Objective To study an improved isolated method of single human atrial myocytes.Methods Enzyme digestion method was used to isolate single myocytes from human atrial and whole-cell patch clamp technique was used to record small conductance calcium activated potassium current.Results This method obtained a large number of atrial myocytes.The total amount of atrial myocytes in SR group was 320±30 while AF group was 230±20 and the difference was statistically significant(P<0.01).In this study,a large number of simple and striated single atrial myocytes were obtained,and a typical small-conductance calcium-activated potassium channel current was recorded on the isolated atrial myocytes.Conclusion The established isolated method is simple,stable and effective.We can acquire a large amount of single atrial myocytes with good quality.

BACKGROUND:It is a great potential study that calcium sulfate product loaded with antibiotics is developed, but this product is not systematicaly studied and its biocompatibility and security need to be further studied.
OBJECTIVE:To evaluate the biocompatibility and safety of vancomycin- or gentamicin-loaded calcium sulfate bone.
METHODS: (1) Hemolysis test: vancomycin-loaded, gentamicin-loaded calcium sulfate extracts, double distiled water and saline were added into rabbit anticoagulant blood samples. (2) Micronucleus test: vancomycin-loaded and gentamicin-loaded calcium sulfate extracts, cyclophosphamide and normal saline solution were intraperitonealy injected to mice, respectively. (3) Acute toxicity test: vancomycin-loaded and gentamicin-loaded calcium sulfate extracts, and normal saline solution were intraperitonealy injected to mice, respectively. (4) Pyrogen test: the mice were injected vancomycin-loaded and gentamicin-loaded calcium sulfate extractsvia the ear vein. (5) Intradermal stimulation test: vancomycin-loaded and gentamicin-loaded calcium sulfate extracts were respectively injected into the unilateral spine of rabbits, respectively. (6) Intramuscular implantation test: vancomycin-loaded and gentamicin-loaded calcium sulfate extracts were respectively injected to the dorsal muscle of rabbits. (7) Intraosseous implantation test: vancomycin-loaded and gentamicin-loaded calcium sulfate were implanted into the necrotic femoral bone of rabbits.
RESULTS AND CONCLUSION:Both vancomycin-loaded and gentamicin-loaded calcium sulfate products, which have no hemolytic reaction, genetic toxicity, acute toxicity, pyrogen reaction and skin irritation, are considered to have good biocompatibility and safety.