Extracellular Vesicles Contribute to Viral-Induced Hepatocellular Carcinoma: Understanding Their Involvement in Viral Hepatitis and Their Potential as Biomarkers for Early Hepatocellular Carcinoma Detection.

The high global prevalence of hepatitis B and hepatitis C and the poor prognosis of hepatitis B and hepatitis C-associated hepatocellular carcinoma (HCC), necessitates the early diagnosis and treatment of the disease. Recent studies show that cell-to-cell communication via extracellular vesicles (EVs) is involved in the HCC progression. The objective of the following study was to explore the role of EVs in the progression of viral-induced HCC and investigate their potential for the early diagnosis of cancer. First, the mRNA derived from EVs of HCC patients was compared to the mRNA derived from EVs from the healthy controls. Expression analysis of ANGPTL3, SH3BGRL3, and IFITM3 genes from the EVs was done. Afterward, to confirm whether hepatocytes can uptake EVs, HuH7 cells were exposed to EVs, and the expression analysis of downstream target genes (AKT, TNF-α, and MMP-9) in Huh7 cells was done. Transcriptional analysis showed that in the EVs from HCC patients, the expression levels of ANGPTL3, SH3BGRL3, and IFITM3 were significantly increased by 2.62-, 4.3-, and 9.03-folds, respectively. The downstream targets, AKT, TNF-α, and MMP-9, also showed a considerable change of 4.1-, 1.46-, and 5.05-folds, respectively, in Huh7 cells exposed to HCC EVs. In conclusion, the following study corroborates the role of EVs in HCC progression. Furthermore, the significant alteration in mRNA levels of the selected genes demonstrates their potential to be used as possible biomarkers for the early diagnosis of HCC.

Impact and utility of follicular lymphoma GELF criteria in routine care: an Australasian Lymphoma Alliance study.

Follicular Lymphoma (FL) treatment initiation is largely determined by tumor burden and symptoms. In the pre-rituximab era, the Group d'Etude des Lymphomes Folliculaires (GELF) developed widely adopted criteria to identify high tumor burden FL patients to harmonize clinical trial populations. The utilization of GELF criteria (GELFc) in routine therapeutic decision-making is poorly described. This multicenter retrospective study evaluated patterns of GELFc at presentation and GELFc utilization in therapeutic decision-making in newly diagnosed, advanced stage rituximab-era FL. Associations between GELFc, treatment given, and patient survival were analyzed in 300 eligible cases identified between 2002-2019. 163 (54%) had ≥1 GELFc at diagnosis. The presence or cumulative number of GELFc did not predict PFS in patients undergoing watch-and-wait (WW) or those receiving systemic treatment. Of interest, in patients with ≥1 GELFc, 16/163 (10%) underwent initial watch-and-wait (comprising 22% of the watchand- wait cohort). In those receiving systemic therapy +/- radiotherapy, 74/215 (34%) met no GELFc. Our data suggest clinicians are using adjunctive measures to make decisions regarding treatment initiation in a significant proportion of patients. By restricting FL clinical trial eligibility only to those meeting GELFc, reported outcomes may not be applicable to a significant proportion of patients treated in routine care settings.

Antimetastatic effects of Citrus-derived bioactive ingredients: Mechanistic insights.

The growing complexity of metastasis has sparked tremendous interest in unraveling of the underlying mechanisms which play fundamental role in cancer progression and metastasis. Ground-breaking discoveries in metastasis research have greatly enhanced our understanding about intricate nature of metastasis. Bioactive chemicals obtained from citrus fruits have gained noteworthy appreciation because of significant cancer chemopreventive roles. Deregulated oncogenic signaling cascades play central role in metastasis. Emerging evidence has started to shed light on the metastasis inhibitory properties of naringin, naringenin, tangeretin, nobiletin, hesperidin and hesperetin in different cancer cell lines and xenografted mice. Wnt/?-catenin, TGF/SMAD and NOTCH signaling cascades have been shown to play linchpin role in carcinogenesis and metastasis. There is emerging evidence related to pharmacological targeting of Wnt/?-catenin, TGF/SMAD and NOTCH by citrus-derived bioactive components. These findings are indeed encouraging and will enable researchers to gain further insights into pharmacological targeting of oncogenic pathways to inhibit and prevent metastasis.

A comparative analysis of interferons and direct-acting antivirals on the expression of genes involved in hepatitis C pathogenesis.

The discovery of direct-acting antivirals (DAAs) has revolutionized the treatment of hepatitis C worldwide. In contrast, pegylated interferon-alpha (PEG IFN-α), the older regimen, had limited success. However, the effect of DAAs on the expression of immunomodulatory genes involved in liver pathologies remains ambiguous. The objective of this study was to explore and contrast the effects of DAAs and PEG IFN-α on the expression of selected immunomodulatory genes. Fifty individuals were enrolled in the study and they were divided into five categories; healthy individuals, treatment-naive, DAAs-responders, DAAs-nonresponders, and interferon-relapsers. The effect of the therapies on the expression of transforming growth factor-beta (TGF-ß), tumor necrosis factor-alpha (TNF-α), suppressor of cytokine signaling 3 (SOCS-3), copper/zinc superoxide dismutase (Cu/Zn SOD), interleukin 10 (IL-10), and collagen type 1 was analyzed. Expression analysis of the selected genes was done through real time polymerase chain reaction. A significantly increased expression of TGF-ß was observed in the patients who received DAAs or PEG IFN-α, which suggests that patients receiving anti-HCV therapies are prone to developing fibrosis. Moreover, DAAs-nonresponders had higher expression of TNF-α, SOCS-3, and IL-10. The elevated expression of TNF-α and SOCS-3 insinuates that DAAs-nonresponders may develop insulin resistance and steatosis in the future. Finally, in addition to TGF-ß, high expression of collagen was found in interferon relapsers, which suggests that these patients are the most susceptible to developing cirrhosis.

Spectrum of pulmonary fungal pathogens, associated risk factors, and anti-fungal susceptibility pattern among persons with presumptive tuberculosis at Gombe, Nigeria.

Background: Pulmonary mycosis (PM) poses a great diagnostic challenge due to the lack of pathognomonic and radiological features, especially in the absence of mycology laboratory tests. This study was aimed to isolate, phenotypically identify, determine the prevalence of pulmonary fungal pathogens and antifungal susceptibility pattern of isolates of presumptive tuberculosis (PTB) patients attending Federal Teaching Hospital (FTH) Gombe, Nigeria. Methods: After ethical approval, three consecutive early morning sputa were collected from 216 participants with presumptive of PTB attending FTH Gombe, between May 2, 2017 and May 30, 2018. Samples were processed using standard mycological staining, microscopy, sugar biochemistry, and antifungal susceptibility test protocols. Sociodemographic variables and risk factors of pulmonary fungal infection were assessed through structured questionnaires. Pulmonary fungal infection was defined by the positive culture in at least two sputa. PTB was defined by Genexpert® nested polymerase chain reaction. Results: Of the 216 participants, 19.9% had PTB and 73.6% had pulmonary fungal pathogens. Among the isolated pulmonary fungal pathogens, Aspergillus fumigatus made the highest occurrence, while 6.5% had PTB-fungal co-infection. No significant association existed between the prevalence of PM with age and sex of participants (P < 0.05). Cigarette smoking (adjusted odds ratio [aOR] = 15.9 [95% confidence interval (CI): 0.9-268.8]), prolong antibiotic use (aOR = 77.9 [95% CI: 4.7-1283]) and possession of domestic pet (aOR = 77.9 [95% CI: 4.7-1283]) were significant risk factors of PM (P < 0.05). Penicillium citrinum, Mucor spp. and Aspergillus flavus are more susceptible to voriconazole, and Candida albicans was found to be more susceptible to Nystatin. Of the 159 fungal isolates, 92.5% were resistant to fluconazole. Conclusion: Findings from this study revealed high level pulmonary fungal pathogens, especially among PTB patients. A majority of fungal isolates were resistant to fluconazole. It's recommended that persons should do away with or minimize risk factors for pulmonary fungal pathogens identified in this study.

Regulation of signaling pathways by Ampelopsin (Dihydromyricetin) in different cancers: exploring the highways and byways less travelled.

Ampelopsin or Dihydromyricetin is gradually emerging as a high-quality natural product because of its ability to modulate wide-ranging signaling pathways. Ampelopsin (Dihydromyricetin) has been reported to effectively modulate growth factor receptor (VEGFR2 and PDGFRß) mediated signaling,  TRAIL/TRAIL-R pathway, JAK/STAT and mTOR-driven signaling in different cancers. Ampelopsin (Dihydromyricetin) has also been shown to exert inhibitory effects on the versatile regulators which trigger EMT (Epithelial-to-Mesenchymal Transition). Findings obtained from in-vitro studies are encouraging and there is a need to comprehensively analyze how Ampelopsin (Dihydromyricetin) inhibits tumor growth in different cancer models. Better knowledge of efficacy of Ampelopsin (Dihydromyricetin) in tumor bearing mice will be helpful in maximizing its translational potential.

Closed vs. open method of pneumoperitonium at infra-umbilical site in laparoscopic surgery - A comparative study.

OBJECTIVE: To assess the safety profile of closed and open method of pneumoperitonium by comparing access and closure time during laparoscopic surgery and complications. METHODS: This quassi-experimental study was conducted at Bahawal Victoria Hospital, Bahawalpur, Pakistan, from September 15, 2013, to September 15, 2016, and comprised patients who were block-randomised into two equal groups. The first half constituted Group A where pneumoperitonium was created by closed method, while the latter half was designated as Group B where the open method was employed. The two groups were compared for access, closure time and complications. SPSS 23 was used for data analysis. RESULTS: There were 850 patients, with 425(50%) in each of the two groups. The overall mean age was 38.78±5.41 years, and 667(78%) were females. The mean access time in Group A was 6.58±1.78min and in Group B it was 5.49±1.82 min. The mean closure time was 7.60±2.12min in Group A and 6.91±1.40min in Group B (p<0.00). Access problem in Group A was significantly high (p=0.001). Abdominal wall complications were 13(3.05%) in Group A and 24(5.64%) in Group B (p=0.064). Visceral injury happened in 5(1.17%) patients in Group A and 1(0.23%) in Group B (p=0.101). CONCLUSIONS: Open method of pneumoperitoneum was found to be safe and less time-consuming compared to the closed method.

Emerging themes of regulation of oncogenic proteins by Solanum nigrum and its bioactive molecules in different cancers.

Research over the decades has sequentially and systematically provided a near-complete resolution of multifaceted and therapeutically challenging nature of cancer. Drug discovery from plants has enjoyed a renaissance in the past few years. Natural products have provided many of the lead structures, which are currently being used as templates for the design and synthesis of novel compounds with biologically enhanced properties. With the maturity and diversification of technologies, there is a growing need to design high-throughput functional assays for the evaluation of the myriad of compounds being catalogued. This review sheds light on the tumor suppressive properties of Solanum nigrum and its bioactive ingredients. Several worthy of mention include uttroside B, solanine, solamargine, and physalins, which have been tested for efficacy in cancer cell lines and xenografted mice. We have summarized the most recent findings related to S. nigrum-mediated regulation of intracellular protein network in different cancers. α-Solanine, an active component of S. nigrum, is involved in the regulation of microRNA-21 (miRNA-21) (oncogenic) and miRNA-138 (tumor suppressor) in prostate cancer. However, this is the only available evidence that gives us a clue related to the tumor suppressive effects exerted by components of S. nigrum at a posttranscriptional level. More interestingly, S. nigrum and its components exerted inhibitory effects on different pathways including PI3K/AKT, JAK-STAT, VEGF/VEGFR, and matrix metalloproteinases in different cancers. We also provide an overview of new tools, methodologies, and approaches, which will allow researchers to extract as much information as possible out of the tremendous data sets currently being generated. The use of computational tools will be helpful in processing structurally complex natural products and also in prediction of their macromolecular targets.

Bitter gourd (Momordica charantia) as a rich source of bioactive components to combat cancer naturally: Are we on the right track to fully unlock its potential as inhibitor of deregulated signaling pathways.

Research over decades has progressively explored pharmacological actions of bitter gourd (Momordica charantia). Biologically and pharmacologically active molecules isolated from M. charantia have shown significant anti-cancer activity in cancer cell lines and xenografted mice. In this review spotlight was set on the bioactive compounds isolated from M. charantia that effectively inhibited cancer development and progression via regulation of protein network in cancer cells. We summarize most recent high-quality research work in cancer cell lines and xenografted mice related to tumor suppressive role-play of M. charantia and its bioactive compounds. Although M. charantia mediated health promoting, anti-diabetic, hepatoprotective, anti-inflammatory effects have been extensively investigated, there is insufficient information related to regulation of signaling networks by bioactive molecules obtained from M. charantia in different cancers. M. charantia has been shown to modulate AKT/mTOR/p70S6K signaling, p38MAPK-MAPKAPK-2/HSP-27 pathway, cell cycle regulatory proteins and apoptosis-associated proteins in different cancers. However, still there are visible knowledge gaps related to the drug targets in different cancers because we have not yet developed comprehensive understanding of the M. charantia mediated regulation of signal transduction pathways. To explore these questions, experimental platforms are needed that can prove to be helpful in getting a step closer to personalized medicine.