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Article ; Online: Peptide-Drug Conjugates: Design, Chemistry, and Drug Delivery System as a Novel Cancer Theranostic.

Rizvi, Syed Faheem Askari / Zhang, Linjie / Zhang, Haixia / Fang, Quan

ACS pharmacology & translational science

2024 Volume 7, Issue 2, Page(s) 309–334

Abstract: The emergence of peptide-drug conjugates (PDCs) that utilize target-oriented peptide moieties as carriers of cytotoxic payloads, interconnected with various cleavable/noncleavable linkers, resulted in the key-foundation of the new era of targeted ... ...

Abstract	The emergence of peptide-drug conjugates (PDCs) that utilize target-oriented peptide moieties as carriers of cytotoxic payloads, interconnected with various cleavable/noncleavable linkers, resulted in the key-foundation of the new era of targeted therapeutics. They are capable of retaining the integrity of conjugates in the blood circulatory system as well as releasing the drugs at the tumor microenvironment. Other valuable advantages are specificity and selectivity toward targeted-receptors, higher penetration ability, and drug-loading capacity, making them a suitable candidate to play their vital role as promising carrier agents. In this review, we summarized the types of cell-targeting (CTPs) and cell-penetrating peptides (CPPs) that have broad applications in the advancement of targeted drug-delivery systems (DDS). Moreover, the techniques to overcome the limitations of peptide-chemistry for their extensive implementation to construct the PDCs. Besides this, the diversified breakthrough of linker chemistry, and ample knowledge of various cytotoxic payloads used in PDCs in recent years, as well as the mechanism of action of PDCs was critically discussed. The principal aim is to provide scattered and diversified knowledge in one place and to help researchers understand the pinching knots in the science of PDC development, also their progression toward a bright future for PDCs as novel theranostics in clinical practice.
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2575-9108
ISSN (online)	2575-9108
DOI	10.1021/acsptsci.3c00269
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Article ; Online: A new choice for human rabies diagnosis: A case report of metagenomics next-generation sequencing in diagnosis of human rabies.

Pin, Lan / Lutao, Xie / Linjie, Lai / Qunjie, Pan / Weijun, Fang / Wang, Du

Journal of infection and public health

2022 Volume 15, Issue 11, Page(s) 1276–1278

Abstract: Purpose: We report a case of human rabies diagnosed by the metagenomics next-generation sequencing (mNGS). A 59-year-old man developed clinical rabies 20 days after he was bitten by dogs. Treatment included induction of coma initially; rabies vaccine ... ...

Abstract	Purpose: We report a case of human rabies diagnosed by the metagenomics next-generation sequencing (mNGS). A 59-year-old man developed clinical rabies 20 days after he was bitten by dogs. Treatment included induction of coma initially; rabies vaccine was not administered. The patient was treated with propofol, midazolam, recombinant human interferon α2b, ribavirin, and amantadine. Penehyclidine was administrated to relieved the rabies induced pulmonary edema and the salivation. Results: The patient's situation got worse on the 26th day after admition, and died on the 29th day finally. Conclusion: The mNGS might be a new choice for human rabies diagnosis，penehyclidine was effective in decreasing the rabies induced pulmonary edema and the salivation.
MeSH term(s)	Male ; Humans ; Animals ; Dogs ; Middle Aged ; Rabies/diagnosis ; Pulmonary Edema/drug therapy ; Amantadine/therapeutic use ; Ribavirin/therapeutic use ; High-Throughput Nucleotide Sequencing ; Sensitivity and Specificity
Chemical Substances	Amantadine (BF4C9Z1J53) ; Ribavirin (49717AWG6K)
Language	English
Publishing date	2022-10-14
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2467587-8
ISSN	1876-035X ; 1876-0341
ISSN (online)	1876-035X
ISSN	1876-0341
DOI	10.1016/j.jiph.2022.10.003
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Article ; Online: GPR18 and GPR55-related Ligands Serving as Antagonists or Agonists: Current Situation, Challenges and Perspectives.

Zhang, Linjie / Fang, Yiwen / Hang, Sijing / Wu, Wenhui / Sheng, Ruilong / Guo, Ruihua

Medicinal chemistry (Shariqah (United Arab Emirates))

2023 Volume 19, Issue 9, Page(s) 838–847

Abstract: GPCR superfamily, the largest known family of membrane receptors, consists of six classes from A to F. GPR18 and GPR55, δ-branch of A class, had been reported to have no confirmed endogenous ligand and were named as "orphan receptors". Previous studies ... ...

Abstract	GPCR superfamily, the largest known family of membrane receptors, consists of six classes from A to F. GPR18 and GPR55, δ-branch of A class, had been reported to have no confirmed endogenous ligand and were named as "orphan receptors". Previous studies suggest that both GPR18 and GPR55 are possibly related to the migration and proliferation of cancer cells, macrophages and other inflammation-associated immune cells. Thus, they may be potential targets for inflammation, cancer and analgesia therapy. In this paper, we aimed to summarize the chemical structures and bioactivities of the agonists and antagonists of GPR18 and GPR55; moreover, we have briefly discussed the challenges and future perspectives in this field. This review will be beneficial for further design and synthesis of efficient agonists and antagonists towards GPR18 and GPR55- related disease treatment.
MeSH term(s)	Humans ; Receptors, Cannabinoid ; Receptors, G-Protein-Coupled ; Ligands ; Inflammation
Chemical Substances	Receptors, Cannabinoid ; Receptors, G-Protein-Coupled ; Ligands ; GPR18 protein, human ; GPR55 protein, human
Language	English
Publishing date	2023-04-11
Publishing country	Netherlands
Document type	Review ; Journal Article
ISSN	1875-6638
ISSN (online)	1875-6638
DOI	10.2174/1573406419666230406095220
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Article ; Online: Clinical outcomes of liver transplantation in human immunodeficiency virus/hepatitis B virus coinfected patients in China.

Tang, Jianxin / Weng, Ruihui / Fang, Taishi / Zhang, Kangjun / Yan, Xu / Jin, Xin / Xie, Linjie / Zhao, Dong

BMC infectious diseases

2024 Volume 24, Issue 1, Page(s) 383

Abstract: Background: Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of human immunodeficiency virus (HIV) patients. However, Patients coinfected with HIV and hepatitis B virus (HBV) are more likely ... ...

Abstract	Background: Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of human immunodeficiency virus (HIV) patients. However, Patients coinfected with HIV and hepatitis B virus (HBV) are more likely to develop end-stage liver disease (ESLD) than those infected with HBV alone. Consequently, liver transplantation is often required for these patients. This study evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-HBV coinfected patients in China. Methods: We conducted a retrospective analysis on all HIV-HBV coinfected patients that underwent OLT from April 1, 2019 to December 31, 2021 and their outcomes were compared to all HBV monoinfected patients undergoing OLT during the same period. Patient outcomes were determined, including cumulative survival, viral load, CD4 T-cell count and postoperative complications. Results: The median follow-up of HIV recipients was 36 months after OLT (interquartile range 12-39 months). Almost all patients had stable CD4 T-cell count (> 200 copies/ul), undetectable HBV DNA levels, and undetectable HIV RNA load during follow-up. The 1-, 2-, and 3-year posttransplant survival rates were 85.7% for the HIV group (unchanged from 1 to 3 years) versus 82.2%, 81.2%, and 78.8% for the non-HIV group. Cumulative survival among HIV-HBV coinfected recipients was not significantly different from the HBV monoinfected recipients (log-rank test P = 0.692). The percentage of deaths attributed to infection was comparable between the HIV and non-HIV groups (14.3% vs. 9.32%, P = 0.665). Post OLT, there was no significant difference in acute rejection, cytomegalovirus infection, bacteremia, pulmonary infection, acute kidney injury, de novo tumor and vascular and biliary complications. Conclusions: Liver transplantation in patients with HIV-HBV coinfection yields excellent outcomes in terms of intermediate- or long-term survival rate and low incidence of postoperative complications in China. These findings suggest that OLT is safe and feasible for HIV-HBV coinfected patients with ESLD. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300067631), registered 11 January 2023.
MeSH term(s)	Humans ; Coinfection ; End Stage Liver Disease/surgery ; Hepatitis B/epidemiology ; Hepatitis B virus/genetics ; HIV ; HIV Infections/drug therapy ; Liver Transplantation/adverse effects ; Postoperative Complications/etiology ; Retrospective Studies
Language	English
Publishing date	2024-04-08
Publishing country	England
Document type	Clinical Trial ; Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-024-09284-2
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Article ; Online: Impact of ankylosing spondylitis on stroke limited to specific subtypes: Evidence from Mendelian randomization study.

Mei, Jian / Wei, Penghui / Zhang, Linjie / Ding, Haiqi / Zhang, Wenming / Tang, Yusen / Fang, Xinyu

Frontiers in immunology

2023 Volume 13, Page(s) 1095622

Abstract: Background: The relationship between Ankylosing Spondylitis (AS) and the risk of stroke is complex. Therefore, we utilized Two-Sample Mendelian randomization to examine the probable causal link between these two features.: Methods: The genetic ... ...

Abstract	Background: The relationship between Ankylosing Spondylitis (AS) and the risk of stroke is complex. Therefore, we utilized Two-Sample Mendelian randomization to examine the probable causal link between these two features. Methods: The genetic instruments linked to AS were chosen from a summary-level genetic data set from the FinnGen consortium in people of European ancestry (1462 cases and 164,682 controls). Stroke and its subtypes were selected as outcomes, and the MEGASTROKE consortium population was used to identify the genetic associations of AS on stroke (40,585 cases and 406,111 controls), ischemic stroke (IS) (34,217 cases and 406,111 controls), and its subtypes including large artery stroke (LAS) (4373 cases and 146,392 controls), small vessel stroke (SVS) (5386 cases and 192,662 controls), and cardioembolic stroke (CES) (7193 cases and 204,570 controls). Intracerebral hemorrhage (ICH) (1687 cases and 201,146 controls) data set from the FinnGen consortium was also used. To obtain the casual estimates, the inverse variant weighted (IVW) method was mainly used. By examining the heterogeneity and pleiotropy of particular single nucleotide polymorphisms (SNPs), the robustness of the results was also examined. Results: There was no evidence found to prove the correlation between genetically predicted AS and stroke (odds ratio [OR] 1.014; 95% confidence interval [CI] 0.999-1.031; P = 0.063), ICH (OR 1.030; 95% CI 0.995-1.067; P = 0.090), and IS (OR 1.013; 95% CI 0. 998-1.030; P = 0.090). In terms of the different subtypes of IS, there was strong evidence of positive causal inferences on CES (OR 1.051; 95% CI 1.022-1.081; P = 0.001), and suggestive evidence of positive causal inferences on LAS (OR 1.042; 95% CI 1.003-1.082; P = 0.033), while it was not significant for SVS (OR 1.010; 95% CI 0.975-1.047; P = 0.563). Conclusion: This study suggests that the possible causative impact of genetically predicted AS on stroke may be restricted to the CES and LAS subtypes.
MeSH term(s)	Humans ; Mendelian Randomization Analysis ; Spondylitis, Ankylosing/genetics ; Stroke/genetics ; Stroke/epidemiology ; Cerebral Hemorrhage ; Causality ; Ischemic Stroke
Language	English
Publishing date	2023-01-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1095622
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Article ; Online: Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation.

Bankoti, Kamakshi / Wang, Wei / Amonkar, Gaurang M / Xiong, Linjie / Shui, Jessica E / Zhao, Caiqi / Van, Eric / Mwase, Chimwemwe / Park, Jin-Ah / Mou, Hongmei / Fang, Yinshan / Que, Jianwen / Bai, Yan / Lerou, Paul H / Ai, Xingbin

American journal of respiratory cell and molecular biology

2024 Volume 70, Issue 1, Page(s) 26–38

Abstract: Airway basal stem cells (BSCs) play a critical role in epithelial regeneration. Whether coronavirus disease (COVID-19) affects BSC function is unknown. Here, we derived BSC lines from patients with COVID-19 using tracheal aspirates (TAs) to circumvent ... ...

Abstract	Airway basal stem cells (BSCs) play a critical role in epithelial regeneration. Whether coronavirus disease (COVID-19) affects BSC function is unknown. Here, we derived BSC lines from patients with COVID-19 using tracheal aspirates (TAs) to circumvent the biosafety concerns of live-cell derivation. We show that BSCs derived from the TAs of control patients are
MeSH term(s)	Humans ; Epithelial Cells ; COVID-19 ; Stem Cells ; Cell Differentiation/physiology ; Bronchi
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2023-0104OC
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Article ; Online: Identification of Differentially Expressed Genes in COVID-19 and Integrated Bioinformatics Analysis of Signaling Pathways.

Fang, Linjie / Tang, Tingyu / Hu, Mengqi

Genetics research

2021 Volume 2021, Page(s) 2728757

Abstract: Coronavirus disease 2019 (COVID-19) is acutely infectious pneumonia. Currently, the specific causes and treatment targets of COVID-19 are still unclear. Herein, comprehensive bioinformatics methods were employed to analyze the hub genes in COVID-19 and ... ...

Abstract	Coronavirus disease 2019 (COVID-19) is acutely infectious pneumonia. Currently, the specific causes and treatment targets of COVID-19 are still unclear. Herein, comprehensive bioinformatics methods were employed to analyze the hub genes in COVID-19 and tried to reveal its potential mechanisms. First of all, 34 groups of COVID-19 lung tissues and 17 other diseases' lung tissues were selected from the GSE151764 gene expression profile for research. According to the analysis of the DEGs (differentially expressed genes) in the samples using the limma software package, 84 upregulated DEGs and 46 downregulated DEGs were obtained. Later, by the Database for Annotation, Visualization, and Integrated Discovery (DAVID), they were enriched in the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. It was found that the upregulated DEGs were enriched in the type I interferon signaling pathway, AGE-RAGE signaling pathway in diabetic complications, coronavirus disease, etc. Downregulated DEGs were in cellular response to cytokine stimulus, IL-17 signaling pathway, FoxO signaling pathway, etc. Then, based on GSEA, the enrichment of the gene set in the sample was analyzed in the GO terms, and the gene set was enriched in the positive regulation of myeloid leukocyte cytokine production involved in immune response, programmed necrotic cell death, translesion synthesis, necroptotic process, and condensed nuclear chromosome. Finally, with the help of STRING tools, the PPI (protein-protein interaction) network diagrams of DEGs were constructed. With degree ≥13 as the cutoff degree, 3 upregulated hub genes (ISG15, FN1, and HLA-G) and 4 downregulated hub genes (FOXP3, CXCR4, MMP9, and CD69) were screened out for high degree. All these findings will help us to understand the potential molecular mechanisms of COVID-19, which is also of great significance for its diagnosis and prevention.
MeSH term(s)	COVID-19 ; Computational Biology ; Gene Expression Profiling ; Humans ; SARS-CoV-2 ; Signal Transduction ; Transcriptome
Language	English
Publishing date	2021-12-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2412681-0
ISSN	1469-5073 ; 0016-6723
ISSN (online)	1469-5073
ISSN	0016-6723
DOI	10.1155/2021/2728757
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Article ; Online: Rapid identification of SARS-CoV-2 variants using stable high-frequency mutation sites.

Fu, Yu / He, Xiaobai / Fang, Quan / Kong, Fei / Zhang, Yan / Fu, Ting / Chen, Liang / Liu, YanXin / Wang, Zhen / Lyu, Jianxin / Chen, Linjie

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

2024 Volume 132, Issue 5, Page(s) 348–357

Abstract: Respiratory infectious viruses, including SARS-CoV-2, undergo rapid genetic evolution, resulting in diverse subtypes with complex mutations. Detecting and differentiating these subtypes pose significant challenges in respiratory virus surveillance. To ... ...

Abstract	Respiratory infectious viruses, including SARS-CoV-2, undergo rapid genetic evolution, resulting in diverse subtypes with complex mutations. Detecting and differentiating these subtypes pose significant challenges in respiratory virus surveillance. To address these challenges, we integrated ARMS-PCR with molecular beacon probes, allowing selective amplification and discrimination of subtypes based on adjacent mutation sites. The method exhibited high specificity and sensitivity, detecting as low as 10
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; Sensitivity and Specificity ; Mutation
Language	English
Publishing date	2024-03-15
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	93340-5
ISSN	1600-0463 ; 0903-4641
ISSN (online)	1600-0463
ISSN	0903-4641
DOI	10.1111/apm.13388
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Article ; Online: Effects of robot-assisted upper limb training combined with intermittent theta burst stimulation (iTBS) on cortical activation in stroke patients: A functional near-infrared spectroscopy study.

Dai, Lei / Zhang, Wanying / Zhang, Huihuang / Fang, Linjie / Chen, Jianer / Li, Xiang / Yu, Hong / Song, Jianfei / Chen, Shishi / Zheng, Beisi / Zhang, Yujia / Li, Zhongyi

NeuroRehabilitation

2024 Volume 54, Issue 3, Page(s) 421–434

Abstract: Background: The therapeutic effect and mechanism of robot-assisted upper limb training (RT) combined with intermittent theta burst stimulation (iTBS) for stroke patients are unclear.: Objective: The purpose of this study was to evaluate changes in ... ...

Abstract	Background: The therapeutic effect and mechanism of robot-assisted upper limb training (RT) combined with intermittent theta burst stimulation (iTBS) for stroke patients are unclear. Objective: The purpose of this study was to evaluate changes in brain activation after combination therapy and RT alone using functional near-infrared spectroscopy (fNIRS). Methods: Patients were randomly assigned to two groups (iTBS + RT Group, n = 18, and RT Group, n = 18). Training was conducted five times a week for four weeks. fNIRS was used to measure changes in oxyhemoglobin in both the primary motor cortex (M1) and pre-motor and supplementary motor area (pSMA) during affected limb movement. Fugl-Meyer Assessment-Upper Extremity (FMA-UE) was employed for evaluating the function of upper limbs. Results: Thirty-two patients with subacute stroke completed the study. The cortex of both hemispheres was extensively activated prior to treatment in the RT group. After training, overactivation decreased. The brain activation of the combined treatment group transferred to the affected side after the treatment. There was a notable enhancement in the FMA-UE scores for both groups, with the combined group's progress significantly surpassing that of the RT group. Conclusion: RT combined with iTBS can improve the motor function of stroke patients and promote the balance between cerebral hemispheres.
MeSH term(s)	Humans ; Male ; Female ; Spectroscopy, Near-Infrared/methods ; Middle Aged ; Stroke Rehabilitation/methods ; Upper Extremity/physiopathology ; Robotics ; Transcranial Magnetic Stimulation/methods ; Stroke/physiopathology ; Stroke/therapy ; Aged ; Motor Cortex/physiopathology ; Adult ; Combined Modality Therapy ; Treatment Outcome
Language	English
Publishing date	2024-04-19
Publishing country	Netherlands
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1087912-2
ISSN	1878-6448 ; 1053-8135
ISSN (online)	1878-6448
ISSN	1053-8135
DOI	10.3233/NRE-230355
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Article ; Online: Unraveling the role of CD24 in Hepatocellular carcinoma: Involvement of inactivated Hippo signaling and SOX4-mediated regulation.

He, Xiaobai / Zhang, Yangyang / Fang, Quan / Sun, Yue / Zheng, Xiaoguang / Fu, Yu / Fan, Weijiao / Yang, Leixiang / Hong, Yeting / Du, Yaoqiang / Wang, Zhen / Chen, Linjie

Biochimica et biophysica acta. Molecular basis of disease

2024 Volume 1870, Issue 4, Page(s) 167117

Abstract: Hepatocellular carcinoma (HCC) is a prevalent type of liver cancer, and CD24 gene is reportedly involved in HCC progression. However, the precise regulatory mechanisms of CD24 in HCC remain unclear. In this study, we established a primary HCC mouse model ...

Abstract	Hepatocellular carcinoma (HCC) is a prevalent type of liver cancer, and CD24 gene is reportedly involved in HCC progression. However, the precise regulatory mechanisms of CD24 in HCC remain unclear. In this study, we established a primary HCC mouse model and observed that CD24, induced by inactivation of the Hippo pathway, was highly expressed in HCC. Using a systematic molecular and genomic approach, we identified the Hippo-YAP1-SOX4 pathway as the mechanism through which YAP1 induces CD24 upregulation in HCC cells. CD24 knockdown significantly attenuated YAP1 activation-induced HCC. These findings shed light on the link between CD24 and HCC progression, particularly in the Hippo-inactivated subclass of HCC. Therefore, CD24 may serve as a potential target for specific treatment of this HCC subclass.
MeSH term(s)	Animals ; Mice ; Liver Neoplasms/pathology ; Carcinoma, Hepatocellular/pathology ; Hippo Signaling Pathway ; Cell Line, Tumor ; Up-Regulation
Language	English
Publishing date	2024-03-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2024.167117
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