ObjectiveTo explore the therapeutic mechanism of Buchong Tiaojing prescription for rats with diminished ovarian reserve （DOR） from the perspectives of nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） inflammasome and ferroptosis. MethodsA total of 48 female SD rats were randomly divided into a normal group， a model group， low， medium， and high dose groups of Buchong Tiaojing prescription， and an MCC950 group， with eight rats in each group. Except the normal group， all the other groups were injected subcutaneously on the back of the neck with D-galactose to prepare the DOR rat model. From the 15th day of modeling， the rats in the low， medium， and high dose groups of Buchong Tiaojing prescription were subjected to gavage daily at doses of 14.4， 28.8， 57.6 g·kg^-1， respectively. Rats in the MCC950 group were injected intraperitoneally with MCC950 at a dose of 10 mg·kg^-1， once every other day. The interventions of all the groups lasted for 4 weeks. The estrous cycle of the rats was observed with vaginal exfoliated cell smear. Hematoxylin-eosin （HE） staining was performed to observe the development of follicles and corpus luteum in the ovary. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of serum sex hormones and interleukin-1β （IL-1β）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot assay were performed to detect the mRNA and protein expression of NLRP3 inflammasome， acyl-CoA synthetase long-chain family member 4 （ACSL4）， transferrin receptor 1 （TFR1）， and glutathione peroxidase 4 （GPX4）， and oxidative stress kits were used to detect ovarian superoxide dismutase （SOD） and malondialdehyde （MDA） levels. ResultsDuring the experiment， one rat died in the high dose group of Buchong Tiaojing prescription， and a total of 47 rats were finally included in the index tests and statistics. Compared with those in the normal group， rats in the model group had significantly disturbed estrous cycles， increased number of atretic follicles， and significant disorder of serum sex hormones. The mRNA and protein expression of NLRP3 inflammasome， ACSL4， and TFR1 in ovarian tissue was up-regulated （P<0.01）， while that of GPX4 was significantly down-regulated （P<0.01）. The SOD content in the ovary was decreased significantly， while the MDA level was increased （P<0.01）. After drug intervention， the estrous cycle of rats was basically resumed， and the follicles at all levels were more structurally intact and significantly increased in number. Additionally， the levels of serum sex hormones and IL-1β were significantly improved. The mRNA and protein expression of NLRP3 inflammasome， ACSL4， and TFR1 were down-regulated， while that of GPX4 was significantly up-regulated， and the ovarian oxidative stress was alleviated （P<0.05， P<0.01）， especially in the high dose group of Buchong Tiaojing prescription and the MCC950 group. ConclusionInflammatory injury and ferroptosis occur in the ovaries of DOR rats， and the Buchong Tiaojing prescription is able to inhibit ovarian NLRP3 inflammasome， alleviate the degree of ovarian ferroptosis， and improve ovarian reserve.

ObjectiveTo explore the regulatory effect of Ganluqingwen prescription on inflammation and immunity by observing the clinical efficacy of Ganluqingwen prescription in the treatment of community-acquired pneumonia （CAP）， so as to provide a clinical basis for the treatment of CAP by traditional Chinese medicine （TCM）. MethodsA randomized controlled trial was conducted by selecting patients who were diagnosed with CAP and identified as wind-heat attacking lungs in Xinjiang Uygur Autonomous Region Hospital of TCM from January 2024 to May 2024 and assigning the patients to a control group （treated by western medicine treatment） or an experimental group （treated by Ganluqingwen prescription combined with western medicine）. The data of the enrolled patients before treatment， for three-day treatment， for seven-day treatment， and for 14-day treatment were collected， including basic information， medical history， pneumonia severity index （PSI） classification， and distribution and difference of laboratory and imaging information indexes. The peripheral blood specimens were collected from the patients. and the changes of inflammatory factors in peripheral blood were detected by using enzyme-linked immunosorbent assay （ELISA） reagent kits and flow-type multifactor microarrays to evaluate the clinical safety and efficacy of Ganluqingwen prescription in CAP. ResultsCompared with those in the groups before treatment， the total scores of TCM syndromes significantly decreased in both groups （P<0.05）. Compared with those in the control group after treatment， the total scores of TCM syndromes decreased more significantly in the experimental group （P<0.05）. Compared with the control group after treatment， the experimental group displayed a significantly reduced number of days of fever in patients （P<0.05）. Compared with those in the groups before treatment， the leukocyte， neutrophil counts， C-reactive protein （CRP）， procalcitonin （PCT）， interleukin （IL）-6， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， creatinine （Cr）， creatine kinase （CK）， and creatine kinase isoenzymes （CK-MB） in both groups decreased （P<0.05） after treatment. Compared with that in the control group after treatment， the decrease of leukocyte， neutrophil counts， CRP， PCT， IL-6， ALT， AST， Cr， CK， and CK-MB was more pronounced in the experimental group （P<0.05）. Compared with those in the group before treatment， the partial pressure of carbon dioxide increased in the experimental group for 3 d of treatment （P<0.05）， and the standard alkali residual， actual alkali residual， standard bicarbonate concentration， and actual bicarbonate concentration increased in the experimental group for 7 d of treatment （P<0.05）. Compared with that in the group before treatment， D-dimer decreased in the control group for 7 d of treatment （P<0.05）. D-dimer and activated partial thromboplastin time （APTT） decreased in the experimental group for 3 d of treatment （P<0.05）， and D-dimer， fibrinogen （FIB）， and APTI significantly decreased in the group for 7 d of treatment （P<0.05）. Compared with the group for 3 d of treatment， the experimental group for 7 d of treatment showed decreased FIB （P<0.05）. Compared with those in the groups before treatment， the levels of inflammatory factors IL-4， IL-10， and IL-13 were elevated in the peripheral blood of the two groups after treatment， and the levels of B lymphocyte chemoattractant （BLC）， interferon gamma-induced protein 10 （IP-10）， tumor necrosis factor-alpha （TNF-α）， interferon-gamma （IFN-γ）， monocyte chemoattractant protein-1 （MCP-1）， CRP， IL-2， IL-6， IL-8， IL-17， IL-22， and IL-23p19 were significantly reduced （P<0.01）. Compared with the control group after treatment， the experimental group exhibited more significant improvement in indexes above （P<0.01）. ConclusionThe group treated by Ganluqingwen prescription combined with western medicine shows more significant effects on reducing total scores of TCM syndromes， lowering the ability of leukocyte and neutrophil counts， decreasing BLC， IP-10， TNF-α， IFN-γ， MCP-1， CRP， IL-2， IL-6， IL-8， IL-17， IL-22， and IL-23p19 in the peripheral blood of the patients， and elevating levels of IL-4， IL-10， and IL-13 than the group treated by western drugs alone.

ObjectiveTo explore the regulatory effect of Ganluqingwen prescription on inflammation and immunity by observing the clinical efficacy of Ganluqingwen prescription in the treatment of community-acquired pneumonia （CAP）， so as to provide a clinical basis for the treatment of CAP by traditional Chinese medicine （TCM）. MethodsA randomized controlled trial was conducted by selecting patients who were diagnosed with CAP and identified as wind-heat attacking lungs in Xinjiang Uygur Autonomous Region Hospital of TCM from January 2024 to May 2024 and assigning the patients to a control group （treated by western medicine treatment） or an experimental group （treated by Ganluqingwen prescription combined with western medicine）. The data of the enrolled patients before treatment， for three-day treatment， for seven-day treatment， and for 14-day treatment were collected， including basic information， medical history， pneumonia severity index （PSI） classification， and distribution and difference of laboratory and imaging information indexes. The peripheral blood specimens were collected from the patients. and the changes of inflammatory factors in peripheral blood were detected by using enzyme-linked immunosorbent assay （ELISA） reagent kits and flow-type multifactor microarrays to evaluate the clinical safety and efficacy of Ganluqingwen prescription in CAP. ResultsCompared with those in the groups before treatment， the total scores of TCM syndromes significantly decreased in both groups （P<0.05）. Compared with those in the control group after treatment， the total scores of TCM syndromes decreased more significantly in the experimental group （P<0.05）. Compared with the control group after treatment， the experimental group displayed a significantly reduced number of days of fever in patients （P<0.05）. Compared with those in the groups before treatment， the leukocyte， neutrophil counts， C-reactive protein （CRP）， procalcitonin （PCT）， interleukin （IL）-6， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， creatinine （Cr）， creatine kinase （CK）， and creatine kinase isoenzymes （CK-MB） in both groups decreased （P<0.05） after treatment. Compared with that in the control group after treatment， the decrease of leukocyte， neutrophil counts， CRP， PCT， IL-6， ALT， AST， Cr， CK， and CK-MB was more pronounced in the experimental group （P<0.05）. Compared with those in the group before treatment， the partial pressure of carbon dioxide increased in the experimental group for 3 d of treatment （P<0.05）， and the standard alkali residual， actual alkali residual， standard bicarbonate concentration， and actual bicarbonate concentration increased in the experimental group for 7 d of treatment （P<0.05）. Compared with that in the group before treatment， D-dimer decreased in the control group for 7 d of treatment （P<0.05）. D-dimer and activated partial thromboplastin time （APTT） decreased in the experimental group for 3 d of treatment （P<0.05）， and D-dimer， fibrinogen （FIB）， and APTI significantly decreased in the group for 7 d of treatment （P<0.05）. Compared with the group for 3 d of treatment， the experimental group for 7 d of treatment showed decreased FIB （P<0.05）. Compared with those in the groups before treatment， the levels of inflammatory factors IL-4， IL-10， and IL-13 were elevated in the peripheral blood of the two groups after treatment， and the levels of B lymphocyte chemoattractant （BLC）， interferon gamma-induced protein 10 （IP-10）， tumor necrosis factor-alpha （TNF-α）， interferon-gamma （IFN-γ）， monocyte chemoattractant protein-1 （MCP-1）， CRP， IL-2， IL-6， IL-8， IL-17， IL-22， and IL-23p19 were significantly reduced （P<0.01）. Compared with the control group after treatment， the experimental group exhibited more significant improvement in indexes above （P<0.01）. ConclusionThe group treated by Ganluqingwen prescription combined with western medicine shows more significant effects on reducing total scores of TCM syndromes， lowering the ability of leukocyte and neutrophil counts， decreasing BLC， IP-10， TNF-α， IFN-γ， MCP-1， CRP， IL-2， IL-6， IL-8， IL-17， IL-22， and IL-23p19 in the peripheral blood of the patients， and elevating levels of IL-4， IL-10， and IL-13 than the group treated by western drugs alone.

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

AIM: To investigate the changes of microRNA-34a(miR-34a)and microRNA-29b(miR-29b)levels in lens epithelial cells of age-related cataracts(ARC)patients and their clinical significance.METHODS: A total of 65 ARC patients(study group)and 53 cases of clear lens anterior capsulorhexis(control group)who visited our hospital from February 2023 to February 2024 were gathered. Pearson was applied to test the correlation between miR-34a and miR-29b. Multifactor Logistic regression was applied to determine the factors affecting the occurrence of ARC.RESULTS: Compared with the control group, the expression levels of miR-34a and miR-29b in lens epithelial cells of the research group showed a significant decrease trend(all P<0.05). There was a positive correlation between miR-34a and miR-29b in the lens epithelial cells of ARC patients(r=0.472, P<0.05). MiR-34a and miR-29b were influence factors for ARC(all P<0.05).CONCLUSION: The levels of miR-34a and miR-29b in lens epithelial cells of ARC patients are significantly reduced, which is associated with the occurrence of ARC.

TFIIB-related factor 1 (BRF1) is an important transcription factor. It specifically regulates the transcription of RNA polymerase III-dependent genes (RNA Pol III genes). The products of these genes are some small non-coding RNAs, including transfer RNAs (tRNAs) and 5S ribosomal RNAs (5S rRNA). The transcription levels of tRNAs and 5S rRNA vary with changes in intracellular BRF1 amounts. tRNAs and 5S rRNA play a crucial role in determining protein synthesis. Studies have demonstrated that dysregulation of tRNAs and 5S rRNA is closely related to cell growth, proliferation, transformation, and even tumorigenesis. BRF1 is a key factor determining the generation of tRNAs and 5S rRNA. Increasing BRF1 expression enhances cell proliferation and transformation, promoting tumor development. In contrast, repressing BRF1 activity decreases the rates of cell proliferation and transformation, and inhibits tumor growth. High levels of BRF1 are found in the samples of patients suffering from hepatocellular carcinoma, breast cancer, gastric carcinoma, lung cancer, prostate carcinoma, and other cancers. It indicates that high levels of BRF1 are closely related to the occurrence of human cancer and may be a common landmark of tumors. But there is discrepancy in the regulatory mechanisms and signaling pathways of BRF1 overexpression in different cancers. In general, high levels of BRF1 in patients suffering from cancer show short survival period and poor prognosis. However, there is one exception, namely breast cancer. Approximate 80% of cases of breast cancer are estrogen receptor-positive (ER+) and 20% are ER-. The cases with high levels of BRF1 reveal longer survival period and better prognosis after they accepted the hormone treatment by Tamoxifen (Tam), compared to the cases with low level BRF1. It seems like a contradiction. Most of the cases with high levels of BRF1 belong to ER+ status. Tam has been used to treat ER+ cases of breast cancer after diagnosis and surgery. Thus, hormone therapy, such as Tam, is more effective on these patients. This is because, on one hand, that Tam competes with E2 (17β-estradiol) to bind to estrogen receptor α (ERα), but does not dissociate to occupy the receptors, blocking E2 binding to this receptor and inhibiting its biological effects. On other hand, Tam can inhibit the expression of BRF1, leading to a decline of intracellular BRF1 levels. Therefore, the actual levels of BRF1 are lower in the patients with ER+ breast cancer. It appears the prognosis of the high BRF1 expression cases better than that of the low BRF1 expression cases. Myocardial hypertrophy manifests magnification of cardiomyocyte volume rather than number increasing in the postnatal heart. Myocardial hypertrophy is a critical risk factor underlying cardiovascular diseases. No matter how myocardial hypertrophy occur, it will ultimately lead to myocardial dysfunction and heart failure. Hypertrophic growth of cardiomyocytes requires a large amount of protein synthesis to meet its needs of cardiomyocyte growth. Animal models and cell experiments have shown that myocardial hypertrophy stimulates a significant increase in BRF1 expression and transcription of tRNAs and 5S rRNA. Interestingly, elevated levels of BRF1 are found in the myocardium tissues of patients with myocardial hypertrophy. These studies demonstrate that BRF1 indeed plays a critical role in myocardial hypertrophy. In summary, high levels of BRF1 are found in patients suffering from different cancers and myocardial hypertrophy. It implies that BRF1 is a promising biological target of cancer and cardiomyopathy. BRF1 is expected to become a common biomarker for early diagnosis and prognostic observation of different human cancers. It is also an important biomarker for the diagnosis and treatment of cardiomyopathy. BRF1 not only holds an important position in the field of basic medical research but also has great prospects for translational medicine. In the present article, we summarize the progress on studies of BRF1 expressions in cancer and cardiomyopathy, proposes future research directions. It is a new research area. Here, we emphasize the significancy of BRF overexpression in the two huge diseases of human, cancer and cardiomyopathy to raise people's attention to this field.

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals ; PC12 Cells ; Rats ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Corticosterone/adverse effects* ; Membrane Potential, Mitochondrial/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Protective Agents/pharmacology* ; Cell Survival/drug effects*