In silico profiling, docking analysis, and protein interactions of secondary metabolites in Musa spp. Against the SGE1 protein of Fusarium oxysporum f. sp. cubense

Article

Author: Dwiningsih, Yheni ; Bhargva, Prachi ; Purwar, Shalini ; Alkahtani, Jawaher ; Singh, Ravindra Pratap ; Al-hashimi, Abdulrahman ; Al-Hashimi, Abdulrahman ; Khan, Salim ; Sonkar, Preeti

Banana Fusarium Wilt (BFW), caused by Fusarium oxysporum f. sp. cubense (Foc), threatens banana crops globally, with the pathogen's virulence partially regulated by the Sge1 transcription factor, which enhances disease severity. Certain Musa species display resistance to Foc, suggesting inherent genetic traits that confer immunity against Sge1Foc. This study utilized bioinformatics tools to investigate the mechanisms underlying this resistance in Musa accuminata subsp. aalaccensis. Through in silico analyses, we explored interactions between Musa spp. and Foc, focusing on the Sge1 protein. Tools such as Anti-SMASH, AutoDockVina 4.0, STRING, and Phoenix facilitated the profiling of secondary metabolites in Musa spp. and the identification of biosynthetic gene clusters involved in defense. Our results indicate that secondary metabolites, including saccharides, terpenes, and polyketides, are crucial to the plant's immune response. Molecular docking studies of selected Musa metabolites, such as 3-Phenylphenol, Catechin, and Epicatechin, revealed 3-Phenylphenol as having the highest binding affinity to the Sge1Foc protein (-6.7 kcal/mol).Further analysis of gene clusters associated with secondary metabolite biosynthesis in Musa spp. identified key domains like Chalcone synthase, Phenylalanine ammonia-lyase, Aminotran 1-2, and CoA-ligase, which are integral to phenylpropanoid production-a critical pathway for secondary metabolites. The study highlights that the phenylpropanoid pathway and secondary metabolite biosynthesis are vital for Musa spp. resistance to Foc. Flavonoids and lignin may inhibit Sge1 protein formation, potentially disrupting Foc's cellular processes. These findings emphasize the role of phenylpropanoid pathways and secondary metabolites in combating BFW and suggest that targeting these pathways could offer innovative strategies for enhancing resistance and controlling BFW in banana crops. This research lays the groundwork for developing sustainable methods to protect banana cultivation and ensure food security.

01 Oct 2024·Journal of Infection and Chemotherapy

Carbapenem non-susceptibility overcalling by BD phoenix NMIC-500 panel

Article

Author: Kim, Jae Kwon ; Yoo, In Young ; Park, Yeon-Joon ; Seok, Hyun Soo ; Kim, Suhng-Wook ; Ha, Sung-Il

We aimed to assess the accuracy of BD Phoenix for determining carbapenem susceptibility because we observed a decline in carbapenem susceptibility rate from the biannual cumulative data, after we transitioned to the BD Phoenix form Vitek 2 system. Between October 2021 and May 2022, we collected 82 non-duplicated Enterobacterales showing non-susceptible to at least one of the three carbapenems by BD Phoenix. We performed the broth microdilution (BMD) and disk diffusion (DD) according to the CLSI guideline. Compared to BMD, the categorical agreements for ertapenem (ERT), imipenem (IPM) and meropenem (MEPM) was 58.8%, 56.8% and 91.5% for BD Phoenix and it was 85.4%, 89.0%, and 97.6%, respectively, for DD (p value; 0.0001 for ERT and IPM, p value; 0.17 for MEPM). The major errors/minor errors for ERT, IPM, and MEPM were 14.0%/31.7%, 2.94%/40.7%, and 2.56%/6.10%, respectively for BD Phoenix, compared to 0%/14.6%, 0%/9.8%, and 0%/2.5%, for DD. While errors in the BD Phoenix showed tendency towards resistance, those in DD displayed no tendency towards either resistance or susceptibility. With DD, 21 out of the 27 isolates showing susceptible/intermediate/susceptible pattern (ERT/IPM/MEPM) and 13 out of the 16 isolates showing intermediate/susceptible/susceptible pattern (ERT/IPM/MEPM), were correctly categorized by DD. However, for 22 isolates showing resistant/susceptible/susceptible pattern (ERT/IPM/MEPM), only 13 isolates were correctly categorized by DD. In conclusion, to mitigate the risk of overcalling carbapenem non-susceptibility with BD Phoenix, it will be helpful to perform a complementary test using DD and to provide comments on the DD results to clinicians.

News (Medical) associated with Anti-PEM monoclonal antibody(Abeona Therapeutics)

14 Nov 2024

·www.globenewswire.com

ACTG Presents Two Studies Providing Insights Into TB Treatment at Union Conference on Lung Health

LOS ANGELES, Nov. 14, 2024 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, announced two oral presentations on tuberculosis (TB) therapy that took place at The Union Conference on Lung Health 2024, in Bali, Indonesia. The oral presentation “Six Months is a Lot of Time to Lie:” Disclosure and Treatment Preferences Among Participants in a Tuberculosis Therapeutic Trial was presented by Faith Mugodhi, M.Sc., H.S.W., University of Zimbabwe-Clinical Trials Research Centre (UZ-CTRC). The oral presentation High Prevalence of Fluoroquinolone Resistance and katG Mutations in Adult Index Patients in a Multinational MDR-TB Prevention Trial was presented by Soyeon Kim, Sc.D., IMPAACT Senior Statistician, Frontier Science Foundation. “ACTG is honored to share these important findings with the many global stakeholders who are gathered in Indonesia at the Union Conference,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “TB is one of ACTG’s key research priorities, as the disease remains a leading killer worldwide. The knowledge gained from the research presented today has the potential to inform our approach to TB treatment and ultimately improve the experiences of people with TB.” “Six Months is a Lot of Time to Lie:” Disclosure and Treatment Preferences Among Participants in a Tuberculosis Therapeutic Trial was a sub-study that investigated experiences around disclosure and treatment preferences among participants in ACTG 5362. Also known as CLO-FAST, this multi-center treatment-shortening trial for drug-susceptible TB randomized individuals to receive either a three-month regimen containing clofazimine (which can be associated with skin hyperpigmentation) or the six-month standard of care. The sub-study consisted of exploratory, qualitative in-depth interviews with 23 participants undergoing treatment in CLO-FAST from India, Malawi, and Zimbabwe. This presentation reported that all sub-study participants with TB had voluntarily disclosed their TB status to at least one other person. Nearly half of participants (43.5 percent) feared inadvertent disclosure of their status due to their treatment and attendance at the TB clinic; 80 percent (n=8) of these were taking clofazimine. One in five participants reported experiencing stigma or discrimination as a result of inadvertent disclosure, including being treated badly by their families or communities. Today’s presentation also found that participants had different preferences around the kind of treatment they received. Two-thirds (n=15) of participants reported that they would prefer the shortened regimen even if one of the medications led to a change in their skin color, while one-third (n=8) reported a preference for the longer regimen. That preference was associated with anticipation of stigma and beliefs that a longer regimen is more potent against TB. These data suggest that anticipated stigma and pre-existing beliefs may be important in understanding treatment preferences. High Prevalence of Fluoroquinolone Resistance and katG Mutations in Adult Index Patients in a Multinational MDR-TB Prevention Trial is an analysis from the PHOENIx study, an ongoing clinical trial evaluating the efficacy and safety of preventive treatment for multi-drug resistant TB (MDR-TB) with delamanid compared to isoniazid, conducted jointly by the ACTG and IMPAACT (International Maternal Pediatric Adolescent AIDS Clinical Trials) networks. (IMPAACT is a global collaboration of investigators, institutions, community representatives, and other partners, with a mission to improve health outcomes for infants, children, and adolescents as well as pregnant and postpartum people who are impacted by or living with HIV by evaluating novel treatments and interventions for HIV and its complications for tuberculosis and other related complications, through the conduct of high-quality clinical trials.) Knowledge of drug susceptibility in people with active TB is important for the provision of both efficacious treatment for their TB disease and TB preventive treatment for their contacts. This presentation sought to describe drug resistance patterns in adults with MDR-TB whose household members were approached to participate in PHOENIx. Between June 2019 and October 2023, 1,353 adults with documented MDR-TB were enrolled from 28 sites and 13 countries in Africa, Asia, and Central and South America. Among those for whom isoniazid mutation data were available, 73 percent (n=783 of 1078) had high-level resistance (katG mutations). Among the 699 participants who had fluoroquinolone drug-susceptibility testing available, 20 percent (n=139) had fluoroquinolone resistance. These results suggest that it is important to have non-fluoroquinolone options for TB preventive treatment. They also support the relevance of the PHOENIx trial’s evaluation of delamanid vs. isoniazid for TB preventive treatment in high-risk household contacts of adults with MDR-TB. Primary results of the clinical trial are anticipated in 2027. CLO-FAST is led by John Metcalfe, M.D., Ph.D., M.P.H., University of California San Francisco; Samuel Pierre, M.D., Les Centres Gheskio, Haiti; and Kimberly Scarsi, Pharm.D., M.S., University of Nebraska Medical Center and study drugs were supplied by the Global Drug Facility. PHOENIx is jointly conducted by ACTG and IMPAACT and led by Gavin Churchyard M.B.Ch.B., M.Med., Ph.D., The Aurum Institute NPC; Amita Gupta, M.D., M.H.S., Johns Hopkins University; Anneke Hesseling, M.B.Ch.B., M.Sc., Ph.D., Desmond Tutu TB Centre - Stellenbosch University; and Susan Swindells, M.B.B.S., University of Colorado. Delamanid is supplied for PHOENIx by Otsuka Pharmaceutical Company, Ltd. ACTG is led by Dr. Currier and Joseph J. Eron, M.D., University of North Carolina (ACTG Vice-Chair). The studies are sponsored by the National Institute of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. IMPAACT is also funded by NIAID with support and co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH). About ACTGACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at hundreds of locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH. Media Contact:Jenna Conley, ACTGjenna@conleycommunications.net

Clinical StudyClinical Result

13 Jul 2023

·www.biospace.com

Evren Technologies Announces Launch of Revolutionary Phoenix®100 System for Vagus Nerve Stimulation Research

GAINESVILLE, Fla., July 13, 2023 /PRNewswire/ -- Evren Technologies, an innovator in the field of medical neuromodulation devices, today announced the launch of its pioneering Phoenix® 100 System, a state-of-the-art transcutaneous auricular vagus nerve stimulator (taVNS) research tool. Evren Technologies announced the launch of its pioneering Phoenix® CR-100 System, a state-of-the-art research tool. The Phoenix 100 System solves long-standing challenges faced by researchers in the realm of Vagus Nerve Stimulation (VNS). Current research tools are generally large, immobile, or lack the flexibility required to conduct high-quality clinical research. The Phoenix 100 System provides a compact, versatile, and programmable system tailored to the needs of PTSD patients and other indications that may benefit from non-invasive VNS research or treatment. "The launch of our Phoenix 100 System to the research community marks a critical milestone in our journey, further building upon our reputation in the rapidly growing field of bioelectronic medicine. It opens the door to the use of taVNS therapy for the 12 million patients suffering from PTSD in the US and has resulted in our first product revenue!" said Weaver Gaines, Chairman & CEO. The Phoenix 100 stimulates the vagus nerve via the ear's pinna, downregulating the sympathetic nervous system to reduce stress response. As the auricular branch of the vagus nerve primarily contains afferent fibers (going towards the brain), this type of stimulation is hands-free and reduces the risk of side effects, offering a significant advantage over cervical vagus nerve stimulation devices. Designed specifically for VNS research, the Phoenix 100 System comprises a stimulator, a comfortable earpiece, and programming software. The Phoenix 100 System is the first to feature physiological monitoring to ensure stimulation quality, high-quality programmable stimulation with a wide range of amplitude and frequency choices, two calibration options, data logging, remote communication, and an adaptable home study capability. The important adherence monitoring feature in the easy-to-use device ensures that patients are following clinical protocols at home. Anne Favre, MSE, MBA, Evren's COO Protem, explains "Many investigators close the discussion sections of their research with the sentiment 'further research is needed to optimize stimulation parameters, establish standardized protocols, and understand VNS mechanisms of action.' This is why now is the ideal time for the programmable Phoenix 100 System. This launch advances Evren's mission to empower PTSD patients and improve their lives through non-invasive, portable neuromodulation products." About Evren Technologies Evren is an innovator in the field of medical neuromodulation devices and is transforming the treatment of PTSD, Acute Stress Reactions, and Acute Stress Disorder by delivering noninvasive, breakthrough, Vagal Nerve Stimulation (VNS) to the auricular branch of the vagus nerve. Our initial product -- the Phoenix® 100 System – administers transcutaneous auricular VNS (taVNS) safely and effectively in laboratory, clinical, and unsupervised home settings for VNS research use and was launched in June 2023. The Phoenix 100 will also be the clinical trial device in Evren's pivotal trial seeking De Novo classification from the FDA. It will deliver safe and effective taVNS therapy, with no known adverse side effects. Bioelectronic medicine uses sophisticated technology to modulate the electrical activity of the body's nervous system and has the potential to supplement or even replace drugs or other interventions. Evren's technology is based on stimulating the vagus nerve, the main nerve of the parasympathetic ("calming or safety) branch of the autonomic nervous system. For further information about the Phoenix 100 System or Evren Technologies, please visit evrenvns.com. CONTACT: Joshua Kelly, Director of Operations Evren Technologies, Inc. 904.517.2432 Joshua.kelly@evrenvns.com View original content to download multimedia: SOURCE Evren Technologies, Inc.

07 Sep 2022

·endpts.com

Adcomm votes 7-2 in favor of Amylyx's ALS drug on second take. But first the co-CEOs had to make a pledge

Second time’s the charm for Amylyx and its experimental ALS drug. In an unusual twist, outside experts on an FDA advisory committee voted 7-2 in favor of approving AMX0035, just months after voting against the drug in a first adcomm. Even more unusual was a promise from both CDER’s neuroscience director Billy Dunn and Amylyx’s co-CEOs that AMX0035 would be pulled from the market if the drug fails its ongoing Phase III Phoenix trial. “To be clear, if Phoenix is not successful, we will do what is right for patients, which includes voluntarily removing the product from the market,” CEO Justin Klee said. While most adcomm members agreed that the data could be more robust, some swung their votes after seeing additional post-hoc analyses from Amylyx and hearing testimonies from clinicians and patients, a majority of whom advocated for AMX0035’s approval. “To deprive ALS patients from a drug that might work, it’s probably not something I’ll feel terribly comfortable with,” Liana Apostolova, an adcomm member and Indiana University School of Medicine professor, said before filing her ‘yes’ vote. She had previously voted against AMX0035 in March. “In the previous meeting, it wasn’t that clear. It’s still questionable. But I would say cost for a rare disease with such a harsh prognosis, I don’t know if I’ll go there,” she added. The committee had previously voted 6-4 against AMX0035 back in March, deciding that the single randomized Centaur trial was not robust enough to prove efficacy, despite meeting its primary endpoint. However, the FDA granted Amylyx a second adcomm and extended the drug’s PDUFA date by three months after researchers submitted updated analyses as potential confirmatory evidence, including an assessment of patients who switched from treatment to placebo after the Phase II trial concluded, suggesting better survival results. Amylyx also presented a post-hoc analysis comparing patients’ progression in the AMX0035 group to their own progression rates prior to the study, and biomarker data from an Alzheimer’s study to show the drug’s effects on neurodegeneration. FDA reviewers poked holes in the new analyses in briefing documents last week, emphasizing that the data are not new, but rather “simply a new method for analyzing the same survival data presented in the original NDA submission,” and that a Phase III readout is coming in the next couple years. “This places the Agency in a challenging situation of potentially making a regulatory decision that may not be subsequently aligned with the results of the ongoing study,” the briefing documents read. FDA again finds Amylyx's ALS data lacking ahead of unusual second adcomm, while stressing dire need for treatments But while the Phase III Phoenix trial is expected to wrap up in late 2023 or early 2024, Amylyx and other ALS advocates argued that patients don’t have time to wait for a pivotal readout, as the average life expectancy post-diagnosis is just two to five years. “For me, ALS feels like being buried alive,” a patient advocate said during the public hearing portion of the call. “We cannot wait years for the Phoenix trial when people with ALS are looking at a treatment that is safe and effective today. If we wait, many who are living with ALS will no longer be with us.” While Canada granted AMX0035 a conditional approval earlier this year, contingent upon a successful Phase III study, Dunn emphasized that the Canadian approval is based on a threshold of promising evidence rather than substantial evidence. Speaking of which, the FDA adcomm considered a slightly different question this time around, voting on whether the available data are enough to “support approval.” Back in March, they voted on whether study data “established a conclusion” that the drug is effective. While the question on Wednesday represented a higher threshold, the FDA’s prompt encouraged members to consider unmet need “and the seriousness of ALS.” Caleb Alexander, a professor at Johns Hopkins Bloomberg School of Public Health who voted against approval of AMX0035, expressed doubt that Amylyx would actually end up pulling the drug if the Phoenix trial fails. “I also think the FDA, with all due respect, significantly understates the complexity and likelihood of their pulling a product from the market and frankly, I’m not sure it’s ever taken place, although admittedly, in rare cases, manufacturers themselves have made the decision to do so,” he said in explaining his vote. The issue was recently brought into the spotlight when Covis Pharma refused to pull its preterm birth injection Makena after failing a confirmatory trial. The FDA is holding an adcomm next month to review the drug’s accelerated approval. Makena's accelerated approval withdrawal hearing set for October as Covis wants to do more research While Klee acknowledged that there are many ways to define if a trial is “successful,” he boiled it down to this: If the treatment can benefit people, we have a responsibility to deliver it to them as quickly as possible, and if a treatment should not benefit, or the data shows it does not benefit people, whether that’s the whole population or subsets of the population, then we have a responsibility to either withdraw it from the market or work with both regulators and doctors to make sure it’s addressed appropriately. Though he ended up voting ‘yes,’ adcomm member Bryan Traynor, a senior investigator at the NIH’s National Institute for Aging, raised concerns over the potential cost of AMX0035. “My concern would be, are they going to price it so that they recoup their money within the three years until they know whether the Phase III worked or not?” he asked. While it’s unclear what AMX0035 would cost if given a potential approval, Dunn clarified that “cost is not a consideration in our scientific deliberations and decision making.” Klee and co-CEO Josh Cohen declined to comment on the price. AMX0035’s PDUFA date is Sept. 29. The FDA isn’t required to follow the adcomm’s recommendations, but it typically does.

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100 Deals associated with Anti-PEM monoclonal antibody(Abeona Therapeutics)

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 2	US	Somanta Pharmaceuticals, Inc.	-
Breast Cancer	Phase 2	-	Abeona Therapeutics, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


WCLC2013	Not Applicable	Advanced Lung Non-Small Cell Squamous Carcinoma	56	PEM plus CIS	(wmqbhncris) = rrmaydjgai ywbdxozcho (ugxuxgqsdo )	-	30 Oct 2013
WCLC2013	Not Applicable	Advanced Lung Non-Small Cell Carcinoma	74	PEM-containing regimens	(jaogqcrjfn) = avsuqobvvo ztzfgglbtp (enpbjyhynl ) View more	-	29 Oct 2013
NAVoTrial 1 (WCLC2013)	Not Applicable	Metastatic Non-Squamous Non-Small Cell Lung Carcinoma First line	153	NVBo + P	(kjcpfckkbv) = sbuxbegcqg kzjuefrgdl (tpeptctijz, 65.3 - 83.1) View more	-	28 Oct 2013
NAVoTrial 1 (WCLC2013)	Not Applicable		153	PPem + P	(kjcpfckkbv) = gbqegvqycw kzjuefrgdl (tpeptctijz, 62.5 - 87.2) View more	-	28 Oct 2013
ASCO2013	Not Applicable	Advanced Lung Non-Squamous Non-Small Cell Carcinoma	56	PEM plus CIS	(lwbofczsnk) = vkxczfwwuk wsgmxbgdvj (qweudtdyho )	-	20 May 2013
AACR2013	Phase 2	Advanced Lung Adenocarcinoma Maintenance	54	PEM	qxdhygtyei(gvuqwbkklz) = a statistically significant (P<0.001) increase in lymphocyte number was observed in responders qogrmnfoav (opartbkdwq )	-	15 Apr 2013
NAVoTRIAL01 (ASCO2012)	Phase 2	Advanced Lung Non-Small Cell Carcinoma First line	153	NVBo+P	(jfkwvzudcc) = axuscplbim onhfasaxqj (scoewgqsce ) View more	-	20 May 2012
NAVoTRIAL01 (ASCO2012)	Phase 2	Advanced Lung Non-Small Cell Carcinoma First line	153	PPem+P	(jfkwvzudcc) = swwgjmphwh onhfasaxqj (scoewgqsce ) View more	-	20 May 2012
I-04-015 (ASCO2008)	Phase 2	Advanced Lung Non-Squamous Non-Small Cell Carcinoma First line	69	BV, OX, and PEM	(cntvgfrson) = doqjcspabs pjztaikzmy (iravyydtmv, 5.3 - 8.4) View more	Positive	20 May 2008

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Anti-PEM monoclonal antibody(Abeona Therapeutics)

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