Biomedical subjects

K Yang

Publications and source records attributed to K Yang.

At least 127 records · Page 7Linked to original sources

PubMed1999

Prostaglandins and leukotriene B4 are potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 2 activity in human choriocarcinoma JEG-3 cells.

The 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) is responsible for the inactivation of glucocorticoids. This is the predominant isozyme in the human placenta, where it is proposed to protect the fetus from high levels of maternal cortisol. In the present study, we examined the effects of eicosanoids on the activity of 11beta-HSD2 in human choriocarcinoma JEG-3 cells, a well-established model for placental trophoblasts. Treatment of JEG-3 cells for 24 h with either prostaglandin (PG) E2 or F2alpha attenuated 11beta-HSD2 activity ( approximately 40%). Paradoxically, indomethacin, an inhibitor of cyclooxygenases, inhibited (approximately 40%) rather than stimulated the activity of this enzyme. This indicated that the arachidonic acid metabolism may be diverted to other pathway(s), the products of which may inhibit 11beta-HSD2 activity. To determine whether the lipoxygenase pathways were involved, the cells were treated with nordihydroguaretic acid (NDGA), a blocker of all three (5-, 12-, and 15-) lipoxygenases. NDGA caused a 3-fold increase in 11beta-HSD2 activity. To further delineate which specific lipoxygenase pathway was involved, the cells were incubated with zileuton, a selective inhibitor of 5-lipoxygenase. This resulted in a similar increase in 11beta-HSD2 activity, suggesting that the products of this pathway (e.g., leukotrienes) may be involved. Given that leukotriene B4 (LTB4) is the most biologically active product of the 5-lipoxygenase pathway, we treated the cells with LTB4, which inhibited 11beta-HSD2 activity in a time- and dose-dependent manner with a maximal effect (60% reduction) at 10 nM for 9 h. Semiquantitative reverse transcription-polymerase chain reaction analysis revealed that 11beta-HSD2 mRNA levels were not altered by the addition of LTB4, PGE2, or PGF2alpha, indicating an effect at the posttranscriptional level. In conclusion, these results demonstrate that prostaglandins and LTB4 are potent inhibitors of 11beta-HSD2 activity in JEG-3 cells, suggesting that placental 11beta-HSD2 activity is modulated by these locally produced eicosanoids. This is the first time that the products of arachidonic acid metabolism have been found to regulate the activity of 11beta-HSD2.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1999

International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: IV. Therapeutic dose dependence and abuse liability of benzodiazepines in the long-term treatment of anxiety disorders.

Despite decades of relevant basic and clinical research, active debate continues about the appropriate extent and duration of benzodiazepine use in the treatment of anxiety and related disorders. The primary basis of the controversy seems to be concern among clinicians, regulators, and the public about the dependence potential and the abuse liability of benzodiazepines. This article reports systematically elicited judgments on these issues by a representative panel of 73 internationally recognized experts in the pharmacotherapy of anxiety and depressive disorders, a panel which was constituted by a multistage process of peer nomination. The criterion for inclusion at each stage was the nomination by at least two peers as one of the "professionally most respected physicians of the world with extensive experience and knowledge in the pharmacotherapy of anxiety and depressive disorders." Sixty-six respondents (90%) completed a comprehensive questionnaire covering a wide range of topics relevant to the therapeutic use of benzodiazepines and other medications that might be used for the same purposes. Overall, the expert panel judged that benzodiazepines pose a higher risk of dependence and abuse than most potential substitutes but a lower risk than older sedatives and recognized drugs of abuse. There was little consensus about the relative risk of dependence and abuse among the benzodiazepines. Differences between benzodiazepines with shorter and longer half-lives in inducing withdrawal symptoms are much less clear during tapered than during abrupt discontinuation. There was little agreement about the most important factors contributing to withdrawal symptoms and failure to discontinue benzodiazepines. The pharmacologic properties of the medication may be the most important contributors to withdrawal symptoms. In contrast, the clinical characteristics of the patient may be the most important contributors to failure to discontinue medication. The experts' judgment seems to support the widespread use of benzodiazepines for the treatment of bona fide anxiety disorders, even over long periods. The experts generally viewed dependence and abuse liability as clinical issues amenable to appropriate management, as for other adverse events related to therapy. However, more definitive clinical research on the remaining controversial issues is urgently needed to promote optimal patient care.

Anti-Anxiety Agents↗

PubMed1999

Preclinical mouse models for cancer chemoprevention studies.

To aid in identifying the ability of chemopreventive agents to inhibit tumor development, new preclinical in vivo rodent models have recently been developed. Some of the models contain targeted mutations capable of increasing the incidence and progression of neoplastic lesions, whereas in other models dietary nutrients induce preneoplastic lesions in normal mice. These new preclinical models are assisting the analysis of genetic and environmental factors leading to neoplasia, and clinical studies to evaluate the chemopreventive efficacy of specific nutrients and pharmacological agents.

Animals↗

PubMed1999

Expression and role of parathyroid hormone-related protein in human renal proximal tubule cells during recovery from ATP depletion.

Parathyroid hormone (PTH)-related protein (PTHrP) is widely expressed in normal fetal and adult tissues and regulates growth and differentiation in a number of organ systems. Although various renal cell types produce PTHrP, and PTHrP expression in rat proximal renal tubules is upregulated in response to ischemic injury in vivo, the role of PTHrP in the kidney is unknown. To study the effects of injury on PTHrP expression and its consequences in more detail, the immortalized human proximal tubule cell line HK-2 was used in an in vitro model of ATP depletion to mimic in vivo renal ischemic injury. These cells secrete PTHrP into conditioned medium and express the type I PTH/PTHrP receptor. Treatment of confluent HK-2 cells for 2 h with substrate-free, glucose-free medium containing the mitochondrial inhibitor antimycin A (1 microM) resulted in 75% depletion of cellular ATP. After an additional 2 h in glucose-containing medium, cellular ATP levels recovered to approximately 75% of baseline levels. PTHrP mRNA levels, as measured in RNase protection assays, peaked at 2 h into the recovery period (at four times baseline expression). The increase in PTHrP mRNA expression was correlated with an increase in PTHrP protein content in HK-2 cells at 2 to 6 h into the recovery period. Heat shock protein-70 mRNA expression was not detectable under baseline conditions but likewise peaked at 2 h into the recovery period. Treatment of HK-2 cells during the recovery period after injury with an anti-PTHrP(1-36) antibody (at a dilution of 1:250) resulted in significant reductions in cell number and uptake of [3H]thymidine, compared with nonimmune serum at the same titer. Similar results were observed in uninjured HK-2 cells. It is concluded that this in vitro model of ATP depletion in a human proximal tubule cell line reproduces the pattern of gene expression previously observed in vivo in rat kidney after ischemic injury and that PTHrP plays a mitogenic role in the proliferative response after energy depletion.

Adenosine Diphosphate↗

PubMed1999

Genotoxic exposures of potroom workers.

OBJECTIVES: Potroom workers in aluminum reduction plants have increased risks for bladder and lung cancer due to exposure from polycyclic aromatic hydrocarbons (PAH). In this study correlations between measures of the external, internal, and biological effective dose have been studied for PAH. METHODS: Venous blood samples were obtained from 98 male potroom workers and 55 unexposed male blue-collar workers, for the analysis of aromatic adducts to DNA (deoxyribonucleic acid) in lymphocytes, using the 32P-postlabeling technique. 1-Hydroxypyrene in urine was analyzed with high-pressure liquid chromatography. Personal sampling of both particulate and gas phase PAH was performed during a full workday for the potroom workers and for 5 referents. Individual PAH congeners were determined with liquid chromatographic-mass spectrometric and gas chromatographic-mass spectrometric techniques. RESULTS: The respiratory-zone airborne level of the sum of 22 particulate (median 13.2 micro/m3) and the 7 gas phase PAH-congeners (median 16.3 microg/m3) among the potroom workers was a hundred times higher than among the referents. The urinary concentration of 1-hydroxypyrene before work was 30 times higher for the potroom workers (median 3.43 micromol/mol creatinine) than for the referents. Most airborne PAH congeners correlated with the excretion of 1-hydroxypyrene in urine. The frequency of aromatic DNA adducts did not, however, differ between the potroom workers and the referents, and no correlation was found for 1-hydroxypyrene in urine. CONCLUSIONS: Despite an obvious occupational exposure to PAH, no increase in aromatic DNA adducts in lymphocytes was found among the potroom workers.

Adult↗

PubMed1999

32P-postlabelling with high-performance liquid chromatography for analysis of abundant DNA adducts in human tissues.

Abundant complex DNA adducts can be detected in human tissues by a combined 32P-postlabelling and high-performance liquid chromatography (HPLC) method. The HPLC profiles reveal a panorama of nuclease P1-resistant human adducts, which are not among the known human DNA adducts and are suspected of being endogenous. Lipid peroxidation-induced DNA adducts and I-compounds are two possible candidates for these adducts. Therefore, we performed two experiments: one was to identify chromatographically the lipid peroxidation-induced adducts among other human adducts with two acrolein- and crotonaldehyde-derived propano adduct standards (Acr-dG3 and Cro-dG1&2) and a structurally unknown adduct (Cro-DNA) derived from crotonaldehyde-treated DNA; and the other was to analyse the adducts in breast tissue from patients with breast cancer and from controls and to compare their behaviour with that of I-compounds in cancerous tissues. In the first experiment, Acr-dG3 and Cro-dG1 were detected in three human lung tissues, at levels ranging from 3.4 to 8.9 (x 10(-8)) and from not detectable to 2.9 (x 10(-8)), respectively. Acr-dG3 and Cro-DNA were detected in three human colon tissues, at levels of 0.2-0.4 (x 10(-8)) and 1.2-3.4 (x 10(-8)), respectively. In the second experiment, adjacent and tumorous breast tissues from 15 patients with breast cancer (of an average age of 33.4 years) and normal breast tissue from 18 controls (of an average age of 57.3) were analysed for the abundant complex adducts. The total adduct levels in the adjacent and tumorous tissues were lower than in the normal tissues (with medians of 8.0, 11.8 and 13.3 (x 10(-7)), respectively). Significant differences in the adduct levels between adjacent or tumorous tissues and normal tissues were observed in three HPLC peaks, and age was significantly associated with three peaks. These results are consistent with our speculation that the abundant adducts are comprised of lipid peroxidation-induced adducts and human homologues of I-compounds.

Acrolein↗

PubMed1999

[A study on C-erbB2, nm23 and p53 expressions in epithelial ovarian cancer and their clinical significance].

OBJECTIVE: To investigate the expressions of C-erbB2, nm23 and p53 in epithelial ovarian cancer and their clinical significance. METHODS: Expression of C-erbB2, nm23 and p53 proteins was retrospectively studied by immunohistochemistry, and Kaplan-Meier Method and Cox's proportional hazard regression model were used to analyze the relationship of their expressions with prognosis. RESULTS: (1) The expression rate of C-erbB2 was 31.4%, and was in connection with clinical stage. (2) The expression rate of nm23 was 38.6%, while it maybe correlated with pelvic lymph node metastasis. (3) The expression rate of p53 was 34.3%, and the rate was higher in serous ovarian cancer than in mucinous. (4) There was no correlation among the expression of the three proteins. (5) Survival follow-up data showed that mean survival time was shorter in patients with C-erbB2 expression than those without; and nm23 and p53 were not significantly related to survival time. Multivariate Cox's proportional hazard regression model analysis suggest that C-erbB2 expression clinical stage and residual tumor size were three variates significantly contributing to patients prognosis. CONCLUSIONS: C-erbB2 expression has a close relationship with malignancy degree of epithelial ovarian cancer, and significantly contributes to prognosis. p53 expression correlates with its subtype and nm23 with its status of pelvic lymph node metastasis, however, neither contributes to prognosis.

Adult↗

PubMed1999

[Detection of aberrant chromosomes in acute lymphoblastic leukemia by fluorescence in situ hybridization].

OBJECTIVE: To investigate the value of fluorescence in situ hybridization (FISH) in detecting aberrant chromosomes in acute lymphoblastic leukemias. METHODS: Conventional banding techniques and FISH were used to detect trisomy 17, 18 and 21 in 38 patients with acute lymphoblastic leukemia. Lymphoid DNA probes specific for chromosomes no. 17, 18 and 21 were used for FISH. RESULTS: Out of the 38 patients, 18 had + 17, 22 + 18 and 23 + 21. The number of trisomy cells ranged from 7% to 80%. Ten normal bone marrow samples were hybridized with the chromosomes 17, 18 and 21 probes. CONCLUSION: FISH is more sensitive than conventional cytogenetic analysis and allows systematic study on large cohort of patients without the need of metaphase preparations.

Adolescent↗

PubMed1999

[Local expresion of proinflammatory cytokines in maxillofacial gunshot wound].

OBJECTIVE: To study the relationship between proinflammentory cytokines and wound healing in local area. METHODS: Interleukin(IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) expression in local soft tissues after lower jaw gunshot wound were assessed by using immunohisto-chemistry, and pathological methods. RESULTS: High expressions of these cytokines were observed in local soft tissues of wounds after the gunshot. The cytokines expressions were different between the area near the bullet path and that far from the path. There was only one peak of the cytokines concentrations in the area far from the bullet path, while there were two peaks of the cytokines concentrations in the area near the bullet path, specially IL-6, IL-8. There were time differences for some different cytokines to reach the peaks of the their concentrations. In wound situ, the fibroblasts, mononuclear phagocytes and endothelial cells expressed IL-6, IL-8 and TNF-alpha after the firearm. CONCLUSION: These results suggest that proinflammatory cytokines play an important role in regulating inflammatory cytokine reactions of local injury tissues. They might improve the functions of fibroblasts, mononuclear phagocytes and endothelial cells and stimulate wound cells to produce and release other cytokines.

Animals↗

PubMed1999

[TNF-alpha, IL-8 and IL-6 in the early inflammatory stage of experimental PVR model induced by macrophages].

OBJECTIVE: To observe the levels of cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and IL-6 in the early inflammatory stages of a rabbit proliferative vitreoretinopathy (PVR) model induced by macrophages. METHODS: The vitreous and venous blood of rabbit eyes of the PVR model were obtained and tested with ELISA kits of TNF-alpha, IL-8 and IL-6 and analyzed statistically. RESULTS: The TNF-alpha level increased at the 7th day after macrophage injection and reached its peak (309 pg/ml) on day 21. IL-8 and IL-6 maintained their higher levels during 7 to 21 days after macrophage injection and the peak levels were 1 325 pg/ml and 998 pg/ml on day 14 respectively. Those showed significant differences compared to control (P <or= 0.05). CONCLUSION: The 3 cytokines, TNF-alpha, IL-8 and IL-6, present high levels in the early stage and proliferative phase of the PVR model and decrease to normal level in the regeneration (scarring) phase, indicating that these cytokines may play an important role in initiating and modulating the cellular proliferation.

Animals↗

PubMed1999

[Study on cross-sections at the plane of the aortic arch and its adjacent structures].

The purpose of this study was to describe and explain the normal appearances of aortic arch and its adjacent structures on the transaxial sections and to provide anatomical data for the diagnosis of CT and MR images. Dissections were performed on 1.2 cm interval cross-sections of the thorax of 30 embalmed cadavers. The results showed 20.00 +/- 7.30% of the aortic arch and arch of the azygos vein at the same plane and 40.00 +/- 8.94% of the arch of the azygos vein at the level of concavity of the aortic arch. 80.00 +/- 7.30% of the top of the superior aortic recess extended to the level of the aortic arch from which the branchiocephalic trunk arises. At the level of the aortic arch, 100% of the lymph nodes of superior vena cava were located among the aortic arch, superior vena cava and trachea. At the level of azygos vein, 100% of the lymph nodes of azygos vein and the superior aortic recess were located among the superior vena cava, arch of azygos vein, trachea and concavity of aortic arch. These data suggest that aortic arch and arch of azygos vein are the key structures to identify the superior aortic recess and lymph nodes. They are essential for understanding the related pathologic changes depicted on CT and MR images.

Adult↗

PubMed1999

[Study on the molar absorption coefficients of Bi(III)-thiocyanate complexes in UV spectrum].

The absorption spectra of bismuth(II)-thiocyanate in the Tween-80-H2O solution were studied in this paper, in which the maximum wavelength lambdamax = 335 nm and the molar extinction coefficient epsilon335 = 2.61 x 10(4), similar to those of complexes of bismuth with PAR or azoarsenic(III), epsilon610 = 2.70 x 10(4). A new tribasic complex was found and used to explain that bismuth(III)-thiocyanate is a sensitive colour reaction in the Tween-80-H2O solution.

English Abstract↗

PubMed1998

Dietary modulation of carcinoma development in a mouse model for human familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is caused by a dominant mutation in the adenomatous polyposis coli (APC) gene. Individuals with FAP progressively develop adenomas and carcinomas of the colon and rectum. We developed a mouse model for this disorder by genetically modifying the Apc gene. The resulting mice Apc1638 progressively develop neoplasms in the colon and remainder of the gastrointestinal tract. In this study when Apc1638 mice were fed a Western-style diet, they developed an increased incidence of the end point of carcinomas and number of invasive tumors. The findings therefore demonstrated dietary modulation of carcinoma incidence in mice with a targeted mutation providing a model for the study of gene-environment interactions in cancer.

Adenoma↗

PubMed1998

Abundant lipophilic DNA adducts in human tissues.

Lipophilic DNA adducts are a complex group of structurally unidentified DNA adducts present in human DNA which can be extracted to 1-butanol and are well retained in C-18 columns during HPLC analysis. Levels of these lipophilic adducts when determined by 32H-HPLC are high. Their abundance highlights the importance of further study. In this study, the lipophilic adducts were analysed by 32H-HPLC in human lung, lymphocyte, breast, skin, colon and endometrial tissues. Tissue-specific patterns of the adducts were shown and the adduct levels in these tissues were 9.7, 13.8, 8.9, 17. 0, 1.8 and 2.3x10-7, respectively. In order to find the possible sources of the lipophilic DNA adducts, effects of cigarette smoking, occupational exposure to PAHs, and age on adduct levels in lymphocytes were examined by analyzing samples collected from 20 Swedish elderly volunteers with a mean age of 55 (10 smokers and 10 non-smokers) and 20 Swedish younger aluminium and control workers with a mean age of 39. Exposures to cigarette smoke and PAHs did not increase total adduct levels nor the levels of major, individual adducts. The total adduct levels in the elderly volunteers and the younger workers were (13.7+/-4.7)/107 and (13.8+/-8.0)/107, respectively, not influenced by age. But the levels of two major HPLC fractions in the elderly volunteers differed significantly from those in the younger workers (25.1/108 vs. 8.7/108 (P<0.0001), and 15.4/108 vs. 28.5/108 (P<0.01), respectively). These results suggested a possible endogenous origin of some of the lipophilic DNA adducts. In further support of this speculation, by comparing migration properties in HPLC and TLC of human adducts with a standard, we found an adduct in human lung tissue that was putatively induced by 2,3-epoxy-4-hydroxynonenal which is an epoxidation product of 4-hydroxynonenal, a major product of lipid peroxidation.

Adult↗

PubMed1998

Capsaicin facilitates excitatory but not inhibitory synaptic transmission in substantia gelatinosa of the rat spinal cord.

Actions of capsaicin were examined on synaptic transmissions in the substantia gelatinosa (SG) of adult rat spinal cord slices using the whole-cell patch-recording technique. Bath-applied capsaicin at a concentration of 2 microM activated a slow inward current (having an amplitude of 33 pA at -70 mV), which was accompanied by an increase in the frequency of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs; by 234%); these actions were blocked by a capsaicin-receptor antagonist, capsazepine (10 microM). The capsaicin-induced increase in sEPSC frequency was resistant to tetrodotoxin (0.5-1 microM). On the other hand, capsaicin (2 microM) did not affect either glycine- or gamma-aminobutyric acid-mediated spontaneous synaptic transmission. The results indicate that capsaicin enhances excitatory but not inhibitory synaptic transmission, possibly through a direct action on primary afferent terminals in the SG. As the SG has been thought to participate in nociceptive pathway, it is suggested that such a presynaptic action of capsaicin contributes to nociceptive transmissions.

Animals↗

PubMed1998

Functional implications of the 21-24 loop in recombinant prochymosin.

To investigate the role of the 21-24 (pepsin numbering) loop in prochymosin, the amino acid residues GTPP at positions 21 through 24 were replaced with GG, the equivalent loop residues from its homologous protein, penicillopepsin, or SG, GS by site-directed mutagenesis. The mutants except GTPP(21-24)GS could be expressed in Escherichia coli. Activation studies indicated that the refolded prochymosin mutants were capable of undergoing autocatalytic activation to produce pseudochymosin by cleaving its N-terminal 27 amino acid residues at pH 2. The resulting pseudochymosin mutants were able to convert into chymosin at pH 5.5 by further autocatalytic cleavage to remove additional 15 amino acid residues. These results demonstrate that the prochymosin analogs can fold into an active state from an unfolded state and that the pseudochymosin analogs can proceed in the transformation from one active form into another active form. Spectroscopic analyses revealed that after mutation the far UV CD spectrum of prochymosin was considerably modified, showing less negative ellipticity values, and the fluorescence emission intensities of prochymosin and pseudochymosin were remarkably reduced. The stabilities of prochymosin and pseudochymosin, especially, were dramatically decreased. The stabilization energy of prochymosin was reduced by 7-8 kJ/mol. The inactivation temperature of pseudochymosin was decreased by 15-20 degrees C. The wild-type pseudochymosin was stable at pH 1.5 and 6.5, whereas the mutants were completely inactivated at the same pH values. Taken together, it is reasonable to conclude that the 21-24 loop (GTPP) plays an important role in determining the stability of prochymosin and pseudochymosin, although the mutants with mutated loop (GG or SG) still can refold into an active conformation.

Animals↗

PubMed1998

Activation of phosphatidylinositol 3-kinase by brain-derived neurotrophic factor gene transfection in septo-hippocampal cultures.

Brain-derived neurotrophic factor (BDNF) has therapeutic potential for treatment of the injured central nervous system. BDNF induces both differentiation and survival of neurons by binding to trkB receptors. This interaction stimulates the intrinsic tyrosine kinase activity of trkB, initiating a signal cascade involving the phosphorylation of intracellular protein on tyrosine, serine, and threonine residues. The purpose of this investigation was to examine the effects of cationic lipid-mediated gene transfection of BDNF on phosphatidylinositol 3 (PI3)-kinase activity in primary septo-hippocampal cell cultures. Thirty-six hours after BDNF gene transfection in the primary CNS cell culture, PI3-kinase activity was significantly increased. The increased PI3-kinase activity was inhibited by wortmannin, a selective and irreversible inhibitor of PI3-kinase. In addition, wortmannin blocked neurofilament increases induced by BDNF gene transfection. This result suggests a possible role of PI3-kinase activation in neuroprotective effects produced by BDNF gene transfection.

Androstadienes↗

PubMed1998

Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway.

The transforming growth factor beta (TGF-beta) superfamily is a family of multifunctional cytokines that transduce signals via serine/threonine kinase receptors. Recent studies revealed that Mothers against dpp (Mad) in Drosophila and its homologs play important roles in the intracellular signal transduction of the serine/threonine kinase receptors. In mammals, one of the Mad homologs, MADH2 (also termed Smad2), was reported to be a mediator of TGF-beta and activin signaling and was found mutated in some of the colon and lung cancer cases. We describe here the genomic organization of the human MADH2 gene. The gene is composed of 12 exons; 2 exons 1, i.e., exon 1a and 1b, are used separately or in conjunction to form exon 1a-exon 1b-exon 2 alternatively spliced mRNA. The 2 exons 1 are closely located, and the MADH2 mRNAs are transcribed from two promoters in one CpG island. The promoter activity in the 5' upstream sequence was confirmed by the luciferase assay. The 3' end of the mRNA is heterogenous, and we found several polyadenylation signals. Northern blot analysis revealed high expression of the MADH2 mRNA, e.g., in skeletal muscle, heart, and placenta. RT-PCR assay using primers in exons 2 and 4 and direct nucleotide sequencing proved that exon 3 is spliced out in about 10% of MADH2 in human placenta. These data will be valuable for studying the MADH2 function in both normal cells and cancer cells.

Activins↗