Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective To evaluate the efficacy and safety of CT-guided 125I seeds implantation for the treatment of abdominal wall incision metastasis of gastrointestinal malignancies.Methods The clinical data of 17 patients with abdominal wall incision metastasis of gastrointestinal malignancies(17 lesions in total),who received CT guided 125I seeds implantation at the Third Affiliated Hospital of Soochow University of China between January 2011 and December 2021,were collected.The treatment planning system was used to make preoperative planning for CT-guided 125I seeds implantation.Follow-up visit was performed once every 3 months to assess the local control rate,treatment-related adverse effects,and degree of pain relief.Results Successful CT-guided 125I seeds implantation was accomplished for the 17 lesions of gastrointestinal malignant tumor incision metastasis.A total of 372 125I seeds were implanted with an average of 21.9 seeds per lesion.The average prescription dose was 100 Gy per lesion.The average survival time was 9.8 months.CT scan performed at 3 months after first-time implantation showed that among the 17 lesions complete remission was obtained in 3,partial remission in 6,stable disease in 7 and progression in one,with a local control rate of 94.1％.The postoperative 6-month and 12-month local objective remission rates were 63.6％and 33.3％respectively,disease control rates were 100％and 50％respectively.Before treatment 8 patients had local pain,and 3 months after treatment pain relief was observed in 6 patients,and in 2 patients the NRS pain score was decreased by ≥ 2 points.No serious postoperative complications occurred.Conclusion For the treatment of abdominal wall incision metastasis of gastrointestinal metastasis,CT-guided 125I seeds implantation is clinically safe and effective.(J Intervent Radiol,2024,33:655-658)

Objective:To establish a method for determintation of chlorogenic acid and linarin in Yejuhua granules by HPLC.Methods:We applied HPLC methods. The Kromasil 100-5 C18 column (250 mm×4.6 mm,5 μm) was used, the mobile phase was acetonitrile-0.4%H 3PO 4 solution (gradient elution), the flow rate was 1.0 ml/min, the dection wavelenghth was 334 nm and the column temperture was 32 ℃. Results:Chlorogenic acid and buddleoside had good linearity in the ranges of 0.30-1.50 μg ( r2=0.999 1) and 0.12-0.62 μg ( r2=0.999 8), respectively. The average recoveries were 99.70% and 96.67%, with RSD<2%, respectively. Conclusion:The method is simple, rapid, reliable, efficient, and can be used for determination of chlorogenic acid and buddleoside in Yejuhua Granules.

Objective To identify the relationship between nephritis activity, autophagy and inflammation in patients with SLE. Methods Western blot analysis was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3) and P62 in peripheral blood mononuclear cells (PBMCs) of SLE patients with lupus nephritis and non-lupus nephritis patients. Tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) in the serum of SLE patients were determined by ELISA. The correlation between LC3II/LC3I ratio and SLE disease activity score (SLEDAI), urinary protein, TNF-α and IFN-γ levels was analyzed by Pearson method. Results The expression of LC3 was increased and P62 was decreased in SLE patients. TNF-α and IFN-γ were increased in the serum of SLE patients. LC3II/LC3I ratio was positively correlated with SLEDAI (r=0.4560), 24 hour urine protein (r=0.3753), IFN-γ (r=0.5685), but had no correlation with TNF-α (r=0.04 683). Conclusion Autophagy is found in PBMCs of SLE, and the autophagy is correlated with renal damage and inflammation in patients with lupus nephritis.
Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Leukocytes, Mononuclear/metabolism* ; Autophagy-Related Proteins/metabolism* ; Lupus Nephritis/urine* ; Kidney ; Interferon-gamma/metabolism* ; Inflammation/metabolism* ; Lupus Erythematosus, Systemic/metabolism*

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

ObjectiveTo investigate the effect and mechanism of Biejiajian Wan on liver fibrosis by regulating the polarization of macrophages. MethodRaw264.7 cells were cultured in vitro by serum pharmacological method， and the hypoxia model of RAW264.7 cells was established by stimulating RAW264.7 cells with cobalt chloride （CoCl₂）. The cells were randomly divided into blank group， CoCl₂ hypoxia model group （200 mmol·L^-1）， Biejiajian Wan low-dose group （200 mmol·L^-1+0.55 g·kg^-1 Fuzheng Quyu capsules）， medium-dose group （200 mmol·L^-1+1.1 g·kg^-1 Biejiajian Wan）， and high-dose group （200 mmol·L^-1+2.2 g·kg^-1 Biejiajian Wan） and Fuzheng Quyu capsule group （200 mmol·L^-1+0.56 g·kg^-1 Biejiajian Wan）. Cell proliferation was detected by cell counting kit-8 （CCK-8）， and the gene expression of hypoxia inducible factor-1α （HIF-1α）， interleukin-1β （IL-1β） and interleukin-6 （IL-6） in macrophages was detected by real time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of macrophage polarization-related protein and HIF-1α/nuclear factor-kappa B （NF-κB） signaling pathway-related protein was tested by Western blot， and the distribution and expression of NF-κB signaling pathway-related protein and HIF-1α were determined by cell immunofluorescence. ResultCompared with the conditions in the blank group， the proliferation of RAW264.7 cells was inhibited after CoCl₂ stimulation for 24 hours （P<0.05）， the mRNA expression of HIF-1α， IL-1β and IL-6 in the model group were increased （P<0.05）， the protein expression of HIF-1α and M1 macrophage phenotypic proteins IL-6 and tumor necrosis factor-α （TNF-α） was boosted while that of M2 macrophage phenotypic protein interleukin-10 （IL-10） was reduced （P<0.05）， the protein expression of NF-κB p65， phosphorylation （p）-NF-κB p65， phosphorylated NF-κB inhibits protein kinase α/β （p-IKKα/β） and phosphorylated NF-κB inhibits protein α (p-IκBα） was elevated （P<0.05）， the nuclear expression of HIF-1α and NF-κB p65 was promoted. Compared with the conditions in the model group， after 24 hours of treatment with corresponding drug-containing serum， each treatment group promoted the proliferation of RAW264.7 cells （P<0.05）， the mRNA expression levels of HIF-1α， IL-1β and IL-6 in macrophages were reduced （P<0.05）， the protein expression of HIF-1α， IL-6 and TNF-α was decreased， while that of CD163 and IL-10 was increased （P<0.05）， the protein expression of NF-κB p65， p-NF-κB p65， p-IKKα/β and p-IκBα was lowered （P<0.05）， the nuclear expression of HIF-1α and NF-κB p65 was inhibited. ConclusionBiejiajian Wan could modulate the polarization of macrophages， attenuate the injury of macrophage-associated inflammatory response under hypoxia， and thus delay the progression of liver fibrosis， which might be related to its regulation of HIF-1α/NF-κB signaling pathway.

ObjectiveTo observe the effect of surface sensation training on walking function of patients after anterior cruciate ligament reconstruction (ACLR). MethodsFrom January to November, 2021, 56 ACLR inpatients in Beijing Rehabilitation Hospital were randomly divided into control group (n = 28) and experimental group (n = 28). The control group received routine rehabilitation training of 45 minutes a time, while the experimental group received routine rehabilitation training of 30 minutes and surface sensation training of 15 minutes a time, for eight weeks. Their toe-out angle and affected side impulse percentage of plantar seven zones were measured before and after intervention. ResultsThe toe-out angle of both the healthy and the affected sides decreased in both groups after intervention (t > 4.615, P < 0.001), and it was less in the affected side in the experimental group (t = 2.263, P < 0.05). The impulse percentage in heel medial and heel lateral areas increased in both groups after intervention (t > 4.221, P < 0.001), and it was more in the experimental group (t > 3.651, P < 0.01); while the impulse percentage in middle foot, foot intermediate and foot lateral areas decreased in both groups (t > 3.174, P < 0.01), and it was less in foot intermediate and foot lateral areas in the experimental group (t > 2.366, P < 0.05); the impulse percentage decreased in foot medial and toe areas in the experimental group (t > 3.508, P < 0.01), but there was no significant difference between two groups (t < 1.608, P > 0.05). ConclusionSurface sensation training can further improve the foot deflection and distribution of impulse of affected side in patients after ACLR during walking, to normalize the load patterns.