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Open AccessEditorial

Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases

by Hang Fai Kwok

Biomolecules 2020, 10(12), 1674; https://doi.org/10.3390/biom10121674 - 15 Dec 2020

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In the last decade, natural-derived/-based biomolecules have continuously played an important role in novel drug discovery (as a prototype drug template) for potential chronic disease treatment [...] Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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11 pages, 1060 KiB

Open AccessCommunication

Branched-Chain Fatty Acids as Mediators of the Activation of Hepatic Peroxisome Proliferator-Activated Receptor Alpha by a Fungal Lipid Extract

by Garima Maheshwari, Robert Ringseis, Gaiping Wen, Denise K. Gessner, Johanna Rost, Marco A. Fraatz, Holger Zorn and Klaus Eder

Biomolecules 2020, 10(9), 1259; https://doi.org/10.3390/biom10091259 - 31 Aug 2020

Cited by 10 | Viewed by 2483

Abstract

The study aimed to test the hypothesis that monomethyl branched-chain fatty acids (BCFAs) and a lipid extract of Conidiobolus heterosporus (CHLE), rich in monomethyl BCFAs, are able to activate the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Rat Fao cells were incubated [...] Read more.

The study aimed to test the hypothesis that monomethyl branched-chain fatty acids (BCFAs) and a lipid extract of Conidiobolus heterosporus (CHLE), rich in monomethyl BCFAs, are able to activate the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha). Rat Fao cells were incubated with the monomethyl BCFAs 12-methyltridecanoic acid (MTriA), 12-methyltetradecanoic acid (MTA), isopalmitic acid (IPA) and 14-methylhexadecanoic acid (MHD), and the direct activation of PPARalpha was evaluated by reporter gene assay using a PPARalpha responsive reporter gene. Furthermore, Fao cells were incubated with different concentrations of the CHLE and PPARalpha activation was also evaluated by using the reporter gene assay, and by determining the mRNA concentrations of selected PPARalpha target genes by real-time RT-PCR. The reporter gene assay revealed that IPA and the CHLE, but not MTriA, MHD and MTA, activate the PPARalpha responsive reporter gene. CHLE dose-dependently increased mRNA concentrations of the PPARalpha target genes acyl-CoA oxidase (ACOX1), cytochrome P450 4A1 (CYP4A1), carnitine palmitoyltransferase 1A (CPT1A) and solute carrier family 22 (organic cation/carnitine transporter), member 5 (SLC22A5). In conclusion, the monomethyl BCFA IPA is a potent PPARalpha activator. CHLE activates PPARalpha-dependent gene expression in Fao cells, an effect that is possibly mediated by IPA. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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15 pages, 3142 KiB

Open AccessArticle

Evaluation of the In Vitro Oral Wound Healing Effects of Pomegranate (Punica granatum) Rind Extract and Punicalagin, in Combination with Zn (II)

by Vildan Celiksoy, Rachael L. Moses, Alastair J. Sloan, Ryan Moseley and Charles M. Heard

Biomolecules 2020, 10(9), 1234; https://doi.org/10.3390/biom10091234 - 25 Aug 2020

Cited by 27 | Viewed by 4827

Abstract

Pomegranate (Punica granatum) is a well-established folklore medicine, demonstrating benefits in treating numerous conditions partly due to its antimicrobial and anti-inflammatory properties. Such desirable medicinal capabilities are attributed to a high hydrolysable tannin content, especially punicalagin. However, few studies have evaluated [...] Read more.

Pomegranate (Punica granatum) is a well-established folklore medicine, demonstrating benefits in treating numerous conditions partly due to its antimicrobial and anti-inflammatory properties. Such desirable medicinal capabilities are attributed to a high hydrolysable tannin content, especially punicalagin. However, few studies have evaluated the abilities of pomegranate to promote oral healing, during situations such as periodontal disease or trauma. Therefore, this study evaluated the antioxidant and in vitro gingival wound healing effects of pomegranate rind extract (PRE) and punicalagin, alone and in combination with Zn (II). In vitro antioxidant activities were studied using DPPH and ABTS assays, with total PRE phenolic content measured by Folin–Ciocalteu assay. PRE, punicalagin and Zn (II) combination effects on human gingival fibroblast viability/proliferation and migration were investigated by MTT assay and scratch wounds, respectively. Punicalagin demonstrated superior antioxidant capacities to PRE, although Zn (II) exerted no additional influences. PRE, punicalagin and Zn (II) reduced gingival fibroblast viability and migration at high concentrations, but retained viability at lower concentrations without Zn (II). Fibroblast speed and distance travelled during migration were also enhanced by punicalagin with Zn (II) at low concentrations. Therefore, punicalagin in combination with Zn (II) may promote certain anti-inflammatory and fibroblast responses to aid oral healing. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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21 pages, 3748 KiB

Open AccessArticle

Lipid Modulation in the Formation of β-Sheet Structures. Implications for De Novo Design of Human Islet Amyloid Polypeptide and the Impact on β-Cell Homeostasis

by Israel Martínez-Navarro, Raúl Díaz-Molina, Angel Pulido-Capiz, Jaime Mas-Oliva, Ismael Luna-Reyes, Eustolia Rodríguez-Velázquez, Ignacio A. Rivero, Marco A. Ramos-Ibarra, Manuel Alatorre-Meda and Victor García-González

Biomolecules 2020, 10(9), 1201; https://doi.org/10.3390/biom10091201 - 19 Aug 2020

Cited by 6 | Viewed by 2728

Abstract

Human islet amyloid polypeptide (hIAPP) corresponds to a 37-residue hormone present in insulin granules that maintains a high propensity to form β-sheet structures during co-secretion with insulin. Previously, employing a biomimetic approach, we proposed a panel of optimized IAPP sequences with only one [...] Read more.

Human islet amyloid polypeptide (hIAPP) corresponds to a 37-residue hormone present in insulin granules that maintains a high propensity to form β-sheet structures during co-secretion with insulin. Previously, employing a biomimetic approach, we proposed a panel of optimized IAPP sequences with only one residue substitution that shows the capability to reduce amyloidogenesis. Taking into account that specific membrane lipids have been considered as a key factor in the induction of cytotoxicity, in this study, following the same design strategy, we characterize the effect of a series of lipids upon several polypeptide domains that show the highest aggregation propensity. The characterization of the C-native segment of hIAPP (residues F₂₃-Y₃₇), together with novel variants F₂₃R and I₂₆A allowed us to demonstrate an effect upon the formation of β-sheet structures. Our results suggest that zwitterionic phospholipids promote adsorption of the C-native segments at the lipid-interface and β-sheet formation with the exception of the F₂₃R variant. Moreover, the presence of cholesterol did not modify this behavior, and the β-sheet structural transitions were not registered when the N-terminal domain of hIAPP (K₁-S₂₀) was characterized. Considering that insulin granules are enriched in phosphatidylserine (PS), the property of lipid vesicles containing negatively charged lipids was also evaluated. We found that these types of lipids promote β-sheet conformational transitions in both the C-native segment and the new variants. Furthermore, these PS/peptides arrangements are internalized in Langerhans islet β-cells, localized in the endoplasmic reticulum, and trigger critical pathways such as unfolded protein response (UPR), affecting insulin secretion. Since this phenomenon was associated with the presence of cytotoxicity on Langerhans islet β-cells, it can be concluded that the anionic lipid environment and degree of solvation are critical conditions for the stability of segments with the propensity to form β-sheet structures, a situation that will eventually affect the structural characteristics and stability of IAPP within insulin granules, thus modifying the insulin secretion. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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18 pages, 4519 KiB

Open AccessArticle

Development and Characterization of a Fucoidan-Based Drug Delivery System by Using Hydrophilic Anticancer Polysaccharides to Simultaneously Deliver Hydrophobic Anticancer Drugs

by Yen-Ho Lai, Chih-Sheng Chiang, Chin-Hao Hsu, Hung-Wei Cheng and San-Yuan Chen

Biomolecules 2020, 10(7), 970; https://doi.org/10.3390/biom10070970 - 28 Jun 2020

Cited by 25 | Viewed by 4112

Abstract

Fucoidan, a natural sulfated polysaccharide, which can activate the immune response and lessen adverse effects, is expected to be an adjuvant agent in combination with chemotherapy. Using natural hydrophilic anticancer polysaccharides to simultaneously encapsulate hydrophobic anticancer drugs is feasible, and a reduced side [...] Read more.

Fucoidan, a natural sulfated polysaccharide, which can activate the immune response and lessen adverse effects, is expected to be an adjuvant agent in combination with chemotherapy. Using natural hydrophilic anticancer polysaccharides to simultaneously encapsulate hydrophobic anticancer drugs is feasible, and a reduced side effect can be achieved to amplify the therapeutic efficacy. In this study, a novel type of fucoidan-PLGA nanocarrier (FPN-DTX) was developed for the encapsulation of the hydrophobic anticancer drug, docetaxel (DTX), as a drug delivery system. From the comparison between FPN-DTX and the PLGA particles without fucoidan (PLGA-DTX), FPNs–DTX with fucoidan were highly stable with smaller sizes and dispersed well without aggregations in an aqueous environment. The drug loading and release can be further modified by modulating relative ratios of Fucoidan (Fu) to PLGA. The (FPN 3-DTX) nanoparticles with a 10:3 ratio of Fu:PLGA displayed uniform particle size with higher encapsulation efficiency than PLGA NPs and sustained drug release ability. The biocompatible fucoidan-PLGA nanoparticles displayed low cytotoxicity without drug loading after incubation with MDA-MB-231 triple-negative breast cancer cells. Despite lower cellular uptake than that of PLGA-DTX due to a higher degree of negative zeta potential and hydrophilicity, FPN 3-DTX effectively exerted better anticancer ability, so FPN 3-DTX can serve as a competent drug delivery system. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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18 pages, 2859 KiB

Open AccessArticle

Discovery of Kynurenines Containing Oligopeptides as Potent Opioid Receptor Agonists

by Edina Szűcs, Azzurra Stefanucci, Marilisa Pia Dimmito, Ferenc Zádor, Stefano Pieretti, Gokhan Zengin, László Vécsei, Sándor Benyhe, Marianna Nalli and Adriano Mollica

Biomolecules 2020, 10(2), 284; https://doi.org/10.3390/biom10020284 - 12 Feb 2020

Cited by 9 | Viewed by 2765

Abstract

Kynurenine (kyn) and kynurenic acid (kyna) are well-defined metabolites of tryptophan catabolism collectively known as “kynurenines”, which exert regulatory functions in host-microbiome signaling, immune cell response, and neuronal excitability. Kynurenine containing peptides endowed with opioid receptor activity have been isolated from natural organisms; [...] Read more.

Kynurenine (kyn) and kynurenic acid (kyna) are well-defined metabolites of tryptophan catabolism collectively known as “kynurenines”, which exert regulatory functions in host-microbiome signaling, immune cell response, and neuronal excitability. Kynurenine containing peptides endowed with opioid receptor activity have been isolated from natural organisms; thus, in this work, novel opioid peptide analogs incorporating L-kynurenine (L-kyn) and kynurenic acid (kyna) in place of native amino acids have been designed and synthesized with the aim to investigate the biological effect of these modifications. The kyna-containing peptide (KA1) binds selectively the μ-opioid receptor with a Ki = 1.08 ± 0.26 (selectivity ratio μ/δ/κ = 1:514:10,000), while the L-kyn-containing peptide (K6) shows a mixed binding affinity for μ, δ, and κ-opioid receptors, with efficacy and potency (E_max = 209.7 + 3.4%; LogEC₅₀ = −5.984 + 0.054) higher than those of the reference compound DAMGO. This novel oligopeptide exhibits a strong antinociceptive effect after i.c.v. and s.c. administrations in in vivo tests, according to good stability in human plasma (t_1/2 = 47 min). Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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10 pages, 2982 KiB

Open AccessArticle

Chemical Constituents of the Leaves of Butterbur (Petasites japonicus) and Their Anti-Inflammatory Effects

by Jin Su Lee, Miran Jeong, Sangsu Park, Seung Mok Ryu, Jun Lee, Ziteng Song, Yuanqiang Guo, Jung-Hye Choi, Dongho Lee and Dae Sik Jang

Biomolecules 2019, 9(12), 806; https://doi.org/10.3390/biom9120806 - 29 Nov 2019

Cited by 26 | Viewed by 3861

Abstract

Two new aryltetralin lactone lignans, petasitesins A and B were isolated from the hot water extract of the leaves of butterbur (Petasites japonicus) along with six known compounds. The chemical structures of lignans 1 and 2 were elucidated on the basis [...] Read more.

Two new aryltetralin lactone lignans, petasitesins A and B were isolated from the hot water extract of the leaves of butterbur (Petasites japonicus) along with six known compounds. The chemical structures of lignans 1 and 2 were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Petasitesin A and cimicifugic acid D showed significant inhibitory effects on the production of both prostaglandin E2 (PGE₂) and NO in RAW264.7 macrophages. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by compound 1 in RAW264.7 cells. Furthermore, compounds 1 and 3 exhibited strong affinities with both iNOS and COX-2 enzymes in molecular docking studies. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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11 pages, 1945 KiB

Open AccessEditor’s ChoiceArticle

Identification and Isolation of Active Compounds from Astragalus membranaceus that Improve Insulin Secretion by Regulating Pancreatic β-Cell Metabolism

by Dahae Lee, Da Hye Lee, Sungyoul Choi, Jin Su Lee, Dae Sik Jang and Ki Sung Kang

Biomolecules 2019, 9(10), 618; https://doi.org/10.3390/biom9100618 - 17 Oct 2019

Cited by 13 | Viewed by 4444

Abstract

In type 2 diabetes (T2D), insufficient secretion of insulin from the pancreatic β-cells contributes to high blood glucose levels, associated with metabolic dysregulation. Interest in natural products to complement or replace existing antidiabetic medications has increased. In this study, we examined the effect [...] Read more.

In type 2 diabetes (T2D), insufficient secretion of insulin from the pancreatic β-cells contributes to high blood glucose levels, associated with metabolic dysregulation. Interest in natural products to complement or replace existing antidiabetic medications has increased. In this study, we examined the effect of Astragalus membranaceus extract (ASME) and its compounds 1–9 on glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. ASME and compounds 1–9 isolated from A. membranaceus stimulated insulin secretion in INS-1 cells without inducing cytotoxicity. A further experiment showed that compounds 2, 3, and 5 enhanced the phosphorylation of total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, and activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), which are associated with β-cell function and insulin secretion. The data suggest that two isoflavonoids (2 and 3) and a nucleoside (compound 5), isolated from the roots of A. membranaceus, have the potential to improve insulin secretion in β-cells, representing the first step towards the development of potent antidiabetic drugs. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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17 pages, 7432 KiB

Open AccessArticle

Orientin Induces G0/G1 Cell Cycle Arrest and Mitochondria Mediated Intrinsic Apoptosis in Human Colorectal Carcinoma HT29 Cells

by Kalaiyarasu Thangaraj, Balamuralikrishnan Balasubramanian, Sungkwon Park, Karthi Natesan, Wenchao Liu and Vaiyapuri Manju

Biomolecules 2019, 9(9), 418; https://doi.org/10.3390/biom9090418 - 27 Aug 2019

Cited by 41 | Viewed by 4556

Abstract

Colorectal carcinoma is one of the utmost diagnosed cancer with a steep increase in mortality rate. The incidence has been increasing in developing countries like India due to a westernization life style. Flavonoids have been explored widely for its various pharmacological activity including [...] Read more.

Colorectal carcinoma is one of the utmost diagnosed cancer with a steep increase in mortality rate. The incidence has been increasing in developing countries like India due to a westernization life style. Flavonoids have been explored widely for its various pharmacological activity including antitumor activity. Orientin, an analogue of luteolin (citrus flavonoid) isolated from rooibos and tulsi leaves is also expected to deliver significant antitumor activity similar to that of luteolin. The present study anticipates exploring the antitumor activity of orientin against colorectal carcinoma cells (HT29). Orientin exhibited remarkable cytotoxicity and antiproliferative activity against HT29 cells, which is clearly evident from tetrazolium based cytotoxicity and lactate dehydrogenase release assays. Orientin induce G0/G1 cell cycle arrest and regulates cyclin and cyclin-dependent protein kinases in order to prevent the entry of the cell cycle to the S phase. Annexin V-FITC (V-Fluorescein Isothiocyanate) dual staining reveals the apoptotic induction ability of orientin. The Bcl-2 family proteins along with the inhibitor of apoptotic proteins were regulated and the tumor suppressor p-53 expression have been decreased. In conclusion, our results proposed that orientin could be a potent chemotherapeutic agent against colorectal cancer after ascertaining their molecular mechanisms. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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16 pages, 2179 KiB

Open AccessEditor’s ChoiceArticle

The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models

by David Martínez-García, Marta Pérez-Hernández, Luís Korrodi-Gregório, Roberto Quesada, Ricard Ramos, Núria Baixeras, Ricardo Pérez-Tomás and Vanessa Soto-Cerrato

Biomolecules 2019, 9(8), 361; https://doi.org/10.3390/biom9080361 - 13 Aug 2019

Cited by 21 | Viewed by 4765

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated [...] Read more.

Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated from marine invertebrates that have shown diverse pharmacological activities. Based on these structures, we have recently identified the novel indole-based tambjamine analog 21 (T21) as a promising antitumor agent, which modulates the expression of apoptotic proteins such as survivin. This antiapoptotic protein plays an important role in carcinogenesis and chemoresistance. In this work, we have elucidated the molecular mechanism by which the anticancer compound T21 exerts survivin inhibition and have validated this protein as a therapeutic target in different lung cancer models. T21 was able to reduce survivin protein levels in vitro by repressing its gene expression through the blockade of Janus kinase/Signal Transducer and Activator of Transcription-3 (JAK/STAT3)/survivin signaling pathway. Interestingly, this occurred even when the pathway was overstimulated with its ligand interleukin 6 (IL-6), which is frequently overexpressed in lung cancer patients who show poor clinical outcomes. Altogether, these results show T21 as a potent anticancer compound that effectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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13 pages, 1378 KiB

Open AccessArticle

Discovery and Rational Design of a Novel Bowman-Birk Related Protease Inhibitor

by Yuxi Miao, Guanzhu Chen, Xinping Xi, Chengbang Ma, Lei Wang, James F. Burrows, Jinao Duan, Mei Zhou and Tianbao Chen

Biomolecules 2019, 9(7), 280; https://doi.org/10.3390/biom9070280 - 14 Jul 2019

Cited by 12 | Viewed by 3729

Abstract

Anuran amphibian skin secretions are a rich source of peptides, many of which represent novel protease inhibitors and can potentially act as a source for protease inhibitor drug discovery. In this study, a novel bioactive Bowman-Birk type inhibitory hexadecapeptide of the Ranacyclin family [...] Read more.

Anuran amphibian skin secretions are a rich source of peptides, many of which represent novel protease inhibitors and can potentially act as a source for protease inhibitor drug discovery. In this study, a novel bioactive Bowman-Birk type inhibitory hexadecapeptide of the Ranacyclin family from the defensive skin secretion of the Fukien gold-striped pond frog, Pelophlax plancyi fukienesis, was successfully isolated and identified, named PPF-BBI. The primary structure of the biosynthetic precursor was deduced from a cDNA sequence cloned from a skin-derived cDNA library, which contains a consensus motif representative of the Bowman-Birk type inhibitor. The peptide was chemically synthesized and displayed a potent inhibitory activity against trypsin (Ki of 0.17 µM), as well as an inhibitory activity against tryptase (Ki of 30.73 µM). A number of analogues of this peptide were produced by rational design. An analogue, which substituted the lysine (K) at the predicted P₁ position with phenylalanine (F), exhibited a potent chymotrypsin inhibitory activity (Ki of 0.851 µM). Alternatively, a more potent protease inhibitory activity, as well as antimicrobial activity, was observed when P¹⁶ was replaced by lysine, forming K¹⁶-PPF-BBI. The addition of the cell-penetrating peptide Tat with a trypsin inhibitory loop resulted in a peptide with a selective inhibitory activity toward trypsin, as well as a strong antifungal activity. This peptide also inhibited the growth of two lung cancer cells, H460 and H157, demonstrating that the targeted modifications of this peptide could effectively and efficiently alter its bioactivity. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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12 pages, 3186 KiB

Open AccessArticle

Regulation of the Expression of DAPK1 by SUMO Pathway

by Qingshui Wang, Xiuli Zhang, Ling Chen, Shuyun Weng, Yun Xia, Yan Ye, Ke Li, Ziqiang Liao, Pengchen Chen, Khaldoon Alsamman, Chen Meng, Craig Stevens, Ted R. Hupp and Yao Lin

Biomolecules 2019, 9(4), 151; https://doi.org/10.3390/biom9040151 - 17 Apr 2019

Cited by 6 | Viewed by 3510

Abstract

Death Associated Protein Kinase 1 (DAPK1) is an important signaling kinase mediating the biological effect of multiple natural biomolecules such as IFN-γ, TNF-α, curcumin, etc. DAPK1 is degraded through both ubiquitin-proteasomal and lysosomal degradation pathways. To investigate the crosstalk between these two DAPK1 [...] Read more.

Death Associated Protein Kinase 1 (DAPK1) is an important signaling kinase mediating the biological effect of multiple natural biomolecules such as IFN-γ, TNF-α, curcumin, etc. DAPK1 is degraded through both ubiquitin-proteasomal and lysosomal degradation pathways. To investigate the crosstalk between these two DAPK1 degradation pathways, we carried out a screen using a set of ubiquitin E2 siRNAs at the presence of Tuberous Sclerous 2 (TSC2) and identified that the small ubiquitin-like molecule (SUMO) pathway is able to regulate the protein levels of DAPK1. Inhibition of the SUMO pathway enhanced DAPK1 protein levels and the minimum domain of DAPK1 protein required for this regulation is the kinase domain, suggesting that the SUMO pathway regulates DAPK1 protein levels independent of TSC2. Suppression of the SUMO pathway did not enhance DAPK1 protein stability. In addition, mutation of the potential SUMO conjugation sites on DAPK1 kinase domain did not alter its protein stability or response to SUMO pathway inhibition. These data suggested that the SUMO pathway does not regulate DAPK1 protein degradation. The exact molecular mechanism underlying this regulation is yet to be discovered. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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