Influenza A virus (IAV) has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA), the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Here we reviewed the recent progress in the study of conformational changes of HA during viral fusion process and the development of HA-based IAV entry inhibitors, which may provide a new choice for controlling future influenza pandemics.

HSF1, a conserved heat shock factor, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. To our knowledge, it is not known whether HSF1 regulates viral transcription, particularly HIV-1 and its latent form. Here we reveal that HSF1 extensively participates in HIV transcription and is critical for HIV latent reactivation. Mode of action studies demonstrated that HSF1 binds to the HIV 5′-LTR to reactivate viral transcription and recruits a family of closely related multi-subunit complexes, including p300 and p-TEFb. And HSF1 recruits p300 for self-acetylation is also a committed step. The knockout of HSF1 impaired HIV transcription, whereas the conditional over-expression of HSF1 improved that. These findings demonstrate that HSF1 positively regulates the transcription of latent HIV, suggesting that it might be an important target for different therapeutic strategies aimed at a cure for HIV/AIDS.

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Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of 1-methy-4-phenylpyridinium ion (MPP(+)). Increasing studies have shown that hydrogen sulfide (H(2)S) is an endogenous antioxidant gas. We have hypothesized that MPP(+)-caused neurotoxicity may involve the imbalance of proportion to this endogenous protective antioxidant gas. The aim of this study is to evaluate whether MPP(+) disturbs H(2)S synthesis in PC12 cells, a clonal rat pheochromocytoma cell line, and whether disturbance of H(2)S generation induced by MPP(+) is an underlying mechanism of MPP(+)-induced neurotoxicity. We show that exposure of PC12 cells to MPP(+) causes a significant decrease in H(2)S generation and results in remarkable cell damage. We find that cystathionine-β-synthetase (CBS) is catalyzed in PC12 cells to generate H(2)S, and that both expression and activity of CBS are inhibited by MPP(+) treatment. Exposure of sodium hydrosulfide (NaHS), a donor of H(2)S, extenuates MPP(+)-induced cytotoxicity and ROS accumulation in PC12 cells, while inhibition of CBS by amino-oxyacetate (AOAA) exacerbates the effects of MPP(+). These results indicate that MPP(+) neurotoxicity involves reduction of H(2)S production, which is caused by inhibition of CBS. This study provides novel insights into cell death observed in neurodegenerative disease such as Parkinson's disease.

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Both elevated homocysteine and decreased hydrogen sulfide (H(2)S) are observed in the brains of Alzheimer's disease (AD) patients. Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of homocysteine; however, H(2)S is an endogenous antioxidant gas. Therefore, the aim of this study was to investigate whether the imbalance of proportion to this endogenous protective antioxidant gas is involved in homocysteine-caused neurotoxicity. We show that homocysteine inhibits the generation of endogenous H(2)S and the expression and activity of cystathionine-β-synthetase (CBS), the main enzyme responsible for the generation of H(2)S in PC12 cells. S-Adenosylmethionine, an activator of CBS, not only prevents homocysteine-induced inhibition of endogenous H(2)S production but also attenuates homocysteine-triggered cytotoxicity and accumulation of ROS. We find that activation of ERK1/2 occurs in homocysteine-treated PC12 cells and blockade of ERK1/2 with U0126 abolished the homocysteine-induced cytotoxicity and inhibitory effect on endogenous H(2)S generation. These results indicate that homocysteine neurotoxicity involves reduction of H(2)S production, which is caused by inhibition of CBS and mediated by activation of ERK1/2. Our study suggests a promising future of H(2)S-based therapies for neurodegenerative diseases such as AD.

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Hydrogen sulfide (H2S), produced by cystanthionine-γ-lysase (CSE) in the cardiovascular system, has been suggested to be the third gasotransmitter in addition to nitric oxide (NO) and carbon monoxide (CO). The present study aimed to investigate the role of H2S in ischemic postconditioning (IPO) during the early period of reperfusion. IPO with 6 episodes of 10 sec reperfusion followed by 6 episodes of 10 sec ischemia (IPO 2’) was administered when reperfusion was initiated. Cardiodynamics and the concentration of H2S were measured at 1, 2, 3, 4, 5, 10, 20, 30, 60, 90 and 120 min of reperfusion. Lactate dehydrogenase (LDH) levels and infarct size were determined at the end of the reperfusion. The concentration of H2S was stable during the whole experiment in the control group, whereas it reached a peak at the first minute of reperfusion in the ischemia-reperfusion (IR) group. The concentration of H2S at the first minute of reperfusion in the IPO 2’ group was higher compared to that of the IR group, which correlated with cardioprotection including improved heart contractile function and reduced infarct size and LDH levels. However, the above effects of IPO 2’ were attenuated by pre-treatment with blockade of endogenous H2S production with DL-propargylglycine for 20 min prior to global ischemia. Furthermore, we found that other forms of IPO, IPO commencing at 1 min after reperfusion (delayed IPO) or lasting only for 1 min (IPO 1’), failed to increase the concentration of H2S and protect the myocardium. We conclude that the peak of endogenous H2S in the early reperfusion phase is the key to cardioprotection induced by IPO.