Latest ArticlesTo explore the roles of oxidative stress and apoptosis in the renal deficiency and blood stasis type oligoasthenozoospermia（OAS） model, and to investigate the mechanism of the intervention by the Qi-supplementing, Blood-activating and Essence-nourishing formula.
The rat model of renal deficiency and blood stasis type oligoasthenozoospermia was established by intragastric administration of Gentiana macrophylla polysaccharides (GTW). The rats were randomly divided into the model group, the levocarnitine group, the low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula groups; another 8 rats were randomly selected as the normal control group. The levocarnitine group was intragastrically administered 1.8 mL·kg-1 levocarnitine oral liquid; the low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula groups were given 7.87, 15.75 and 31.50 g·kg-1，respectively; the blank group and the model group were intragastrically administered the same amount of 0.9% NaCl. All 6 groups of rats were administered the drugs once daily and continuously for 28 days. The general conditions of the rats were observed; the testicular and epididymal indices were measured; the sperm quality was detected; the pathological morphology of the testicular tissue was observed by hematoxylin-eosin staining (HE); the activity of reactive oxygen species (ROS), catalase (CAT) and superoxide dismutase (SOD) in the testicular tissue was detected by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of Caspase-3, Bcl-2 and Bax in the testicular tissue were detected by real-time fluorescence quantitative polymerase chain reaction (q-PCR).
The testicular indices of the blank group, model group, low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula group, and the levocarnitine group were (0.83±0.09)%, (0.55±0.10)%, (0.55±0.07)%,(0.71±0.12)%,(0.81±0.08)%, and (0.67±0.07)%, respectively; the epididymal indices were (0.36±0.05)%, (0.24±0.03)%, (0.25±0.04)%, (0.28±0.02)%,(0.35±0.06)%, and (0.28±0.03)%,respectively; the sperm concentrations were (24.11±11.64, 4.65±2.48, 6.75±3.81, 11.60±7.78, 21.72±7.81, 23.22±8.80)×106 sperm·mL-1, respectively; the sperm motility was (86.93±12.00)%, (33.46±16.13)%, (53.01±21.71)%, (63.15±24.35)%, (79.97±10.22)%, and (75.83±25.05)%, respectively; the ROS intensity was 597 926.11±87 518.20, 925 239.02±95 539.79, 846 676.84±64 867.76, 784 277.73±81 354.32, 658 228.04±82 768.68, and 725 740.12±87 846.36, respectively; the CAT activity was (1.40±0.11), (0.56±0.09), (0.77±0.11), (0.95±0.13), (1.15±0.12), and (1.03±0.11) U·mgprot-1, respectively; the SOD activity was (2.41±0.07), (1.65±0.05), (1.79±0.33), (1.90±0.04), and (2.21±0.05), and (2.06±0.04) U·mgprot-1, respectively. the relative expression levels of Bcl-2 mRNA were 1.00±0.04, 0.26±0.02, 0.39±0.04, 0.49±0.02, 0.87±0.02, and 0.66±0.05, respectively; the relative expression levels of Bax mRNA were 1.00±0.05, 1.78±0.07, 1.50±0.04, 1.39±0.02, 1.12±0.04, and 1.27±0.04, respectively; the relative expression levels of Caspase-3 mRNA were 1.00±0.03, 1.95±0.06, 1.81±0.03, 1.68±0.03, 1.18±0.07, and 1.49±0.08, respectively. The above-mentioned indicators of the model group compared with the blank group, the high-dose group compared with the model group, and the L-carnitine group except for the epididymal index compared with the model group, all showed statistically significant differences (P<0.05，P<0.01).
Oxidative stress and cell apoptosis play multiple regulatory roles in the sperm quality and testicular damage of OAS rats. The Qi-supplementing, activating blood, and tonifying essence formula may improve the sperm quality and testicular function of rats by inhibiting oxidative stress and cell apoptosis.
To investigate the protective effect and mechanism of astragaloside Ⅳ (AS-Ⅳ) on intestinal injury and secondary liver injury in rats with ulcerative colitis (UC) induced by trinitrobenzene sulfonic acid (TNBS).
Wistar rats were randomly divided into normal control group, UC model group and AS-Ⅳ experimental low, medium and high dose groups, with 10 rats in each group. The UC rat model was prepared by TNBS enema. AS-Ⅳ (25, 50, 100 mg·kg-1) or sulfasalazine (SASP, 300 mg·kg-1) was administered intragastrically for 6 consecutive days starting from the second day after modeling. The general condition, colonic histopathological score, and liver function of the rats were examined. The levels of inflammatory factors in serum, colon and liver tissues were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of tight junction proteins (ZO-1, Occludin) in colon and antioxidant enzymes in liver tissues were detected by Western blot.
In the normal group, model group, low, medium and high dose experimental groups, the serum TNF-α levels were (246.30±23.39), (308.70±61.39), (279.10±45.76), (240.80±16.61) and (233.60±30.14) pg·mL-1, and the serum IL-1β levels were (23.93±14.82), (82.42±20.84), (69.46±22.23), (40.92±11.21) and (35.42±10.34) pg·mL-1，respectively. The intestinal TNF-α levels were (101.60±11.18), (158.70±23.47), (146.40±17.90), (115.70±21.06) and (91.84±21.57) pg·mL-1, and the intestinal IL-1β levels were (724.60±78.73), (1 043.00±106.32), (836.35±103.35), (774.60±133.68) and (694.50±40.84) pg·mL-1，respectively. The relative expression levels of tight junction protein ZO-1 in colon tissue were 1.01±0.01, 0.48±0.01, 0.46±0.01, 0.61±0.09 and 1.15±0.10, and the relative expression levels of tight junction protein Occludin in colon tissue were 1.00±0.01, 0.64±0.11, 0.57±0.13, 0.73±0.10 and 1.02±0.13，respectively. The levels of TNF-α in liver tissues were (1 727.00±223.70), (2 008.00±220.40), (1 762.00±45.19), (1 723.00±49.45), and (1 680.00±103.10) pg·mg-1, and the levels of IL-1β in liver tissues were (1 317.00±331.40), (2 158.00±730.90), (1 546.00±258.90), (1 806.00±523.40), and (1 121.00±84.62) pg·mg-1. The MDA levels in liver tissues were (0.98±0.15), (1.51±0.29), (1.29±0.30), (1.15±0.12) and (1.06±0.21) nmol·mg-1, the reduced glutathione (GSH) levels in liver tissues were (8.46±0.60), (5.84±0.49), (6.30±0.27), (7.48±0.50) and (8.07±0.60) μmol·gProt-1, the glutathione peroxidase (GSH-PX) levels in liver tissues were (666.90±68.39), (481.00±19.16), (562.80±45.61), (620.20±12.13) and (658.80±18.11) U·mgProt-1.The above indicators in the medium and high dose experimental groups were statistically significant compared with the model group (all P<0.05).
AS-IV can effectively improve intestinal and liver injury in rats with UC induced by TNBS. The mechanism may be related to repairing intestinal mucosal barrier, inhibiting inflammatory response and improving liver antioxidant function.
To investigate the effects of daptomycin (DAP) on the proliferation, apoptosis, and cell cycle of U266 [U266B1] human multiple myeloma cells (U266).
U266 cells were divided into the following groups: normal control group (NC group), DAP 20 μM group (DAP20), DAP 40 μM group (DAP40), DAP 80 μM group (DAP80), BZ 50 nM group (BZ50), and DAP 80 μM + BZ 50 nM group (DAP80+BZ50). U266 cells were treated with varying concentrations of DAP (0, 20, 40, and 80 μM), 50 nM bortezomib (BZ), and combination of DAP (80 μM) plus BZ (50 nM). Effects were assessed using cell counting kit-8 (CCK-8) assays, Western blotting (WB), flow cytometry, and quantitative real-time polymerase chain reaction (qPCR).
At 24 h post-treatment: Cell viability rates were recorded as (97.13±2.51)%, (96.80±3.44)%, (85.48±3.28)%, (81.56±2.09)%, (60.78±2.80)%, and (38.09±2.09)% for DAP alone (0-80 μM), BZ monotherapy, and combinatorial treatment, respectively. Early apoptotic cell proportions measured via flow cytometry showed values of (7.50±0.84)%, (8.20±1.41)%, (9.07±1.22)%, (13.14±2.27)%, (14.51±2.58)%, and (15.17±1.87)% across groups. Proportions of cells in G1 phase were determined to be (33.40±1.48)%, (33.03±2.49)%, (31.50±1.40)%, (38.59±1.54)%, (36.94±1.13)%, and (39.43±1.40)%. Relative expression levels of ribosomal protein S19 (RPS19) mRNA exhibited fold changes of 0.99±0.09, 1.00±0.14, 0.66±0.04, 0.61±0.06, 0.55±0.04, and 0.53±0.07, while corresponding protein levels via WB analysis were 1.08±0.05, 0.97±0.03, 0.90±0.02, 0.87±0.04, 0.89±0.04, and 0.57±0.03. Statistically significant differences (all P<0.001) were observed in BZ50, DAP80, and their combination compared to DAP 0 μM group.
DAP may exert its inhibitory effect on U266 cell proliferation and promote apoptosis by downregulating the expression of RPS19. This study provides a potential therapeutic drug for the treatment of multiple myeloma.
The clinical isolation rate of carbapenem-resistant Acinetobacter baumannii (CRAB) has been increasing year by year, yet effective antimicrobial agents against this pathogen remain severely limited. Sulbactam-durlobactam, a novel β-lactam combination agent, has demonstrated promising in vitro antibacterial activity against CRAB. In May 2023, the U.S. Food and Drug Administration approved its use for patients aged 18 and older to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of the Acinetobacter baumannii-calcoaceticus complex, providing a new therapeutic option. This article reviews the mechanism of action, pharmacokinetics, pharmacodynamics, and clinical studies of sulbactam-durlobactam based on literature, aiming to offer insights for clinical practice.
A 76 years old female patient was hospitalized twice for pulmonary infection and bronchiectasis with infection. During her first admission to the respiratory department for pulmonary infection, she received intravenous cefoperazone sodium/sulbactam sodium combined with bronchodilators for 11 days and was discharged following clinical improvement, with no documented adverse drug reactions (ADRs). During her second presentation to the emergency department for bronchiectasis exacerbation, the patient developed cyanosis and profuse sweating 13 minutes after intravenous cefoperazone/sulbactam administration. Despite successful resuscitation and subsequent transfer to the intensive care unit (ICU), emergency physicians failed to recognize this event as a suspected drug hypersensitivity reaction or document it in the medical records. After 11 days of meropenem therapy and symptomatic management in the ICU, she was transferred back to the respiratory department. Respiratory physicians initiated antibiotic de-escalation by readministering cefoperazone/sulbactam, which precipitated respiratory distress, profuse sweating and systemic discomfort within 19 minutes, followed by loss of consciousness and cardiopulmonary arrest. The patient died after 48 hours of unsuccessful resuscitation. This case serves as a reminder that the sensitization period for drugs can persist from several days to several months. The absence of ADRs with previous use does not entirely preclude the risk of subsequent administration. The recognition of hypersensitivity is critical, necessitating enhanced vigilance among healthcare professionals regarding ADRs. The documentation of ADRs and handover procedures during transfers between departments should not be overlooked to ensure medication safety.
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