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Kinase enzymes play an important role in cellular proliferation, and inhibition of their activity is a major goal of cancer therapy. Protein kinase inhibitors as benzimidazole derivatives can be applied for prevention or treatment of cancers through inhibition of cell proliferation. To evaluate their protein kinase inhibitory effects, as well as the in silico study for active benzimidazole derivatives. Benzimidazole derivatives has presented significant therapeutic potential against several disorders and known to have numerous biological activities (such as antibacterial, antiviral and anti-inflammatory). Benzimidazole derivatives have shown significant potential in the reduction of viral load as well as in enhancing immunity. To forecast absorption, distribution, metabolism, excretion and toxicity, simply known as ADMET and the Lipinski rule of five parameters of the examined substances, the admetSAR and Swiss ADME were used. The ADMET predictions revealed that the compounds had good and safe pharmacokinetic features, making them acceptable for further development as therapeutic candidates in clinical trials. This study primarily focused on blocking 2 key targets of kinase proteins (CDK4/CycD1 and Aurora B). 2-Phenylbenzimidazole has shown the greatest inhibitory potential (with a binding energy of −8.2 kcal/mol) against protein kinase inhibitors. This study results would pave the potential lead medication for anticancer therapeutic strategies. [ABSTRACT FROM AUTHOR]

Fasciola hepatica is a parasitic trematode that infects livestock animals and humans, causing significant health and economic burdens worldwide. The extensive use of anthelmintic drugs has led to the emergence of resistant parasite strains, posing a threat to treatment success. The complex life cycle of the liver fluke, coupled with limited funding and research interest, have hindered progress in drug discovery. Our group has been working in drug development against this parasite using cathepsin proteases as molecular targets, finding promising compound candidates with in vitro and in vivo efficacy. Here, we evaluated hybrid molecules that combine two chemotypes, chalcones and quinoxaline 1,4-di- N-oxides, previously found to inhibit F. hepatica cathepsin Ls and tested their in vitro activity with the isolated targets and the parasites in culture. These molecules proved to be good cathepsin inhibitors and to kill the juvenile parasites at micromolar concentrations. Also, we performed molecular docking studies to analyze the compounds-cathepsins interface, finding that the best inhibitors interact at the active site cleft and contact the catalytic dyad and residues belonging to the substrate binding pockets. We conclude that the hybrid compounds constitute promising scaffolds for the further development of new fasciolicidal compounds., (© 2024 Wiley-VCH GmbH.)

We propose a novel framework, Manticore , for multiparty computations, with full threshold and semi-honest security model, supporting a combination of real number arithmetic (arithmetic shares), Boolean arithmetic (Boolean shares) and garbled circuits (Yao shares). In contrast to prior work (Mohassel and Zhang, in 2017 IEEE symposium on security and privacy (SP), 2017; Mohassel and Rindal, in Proceedings of the 2018 ACM SIGSAC conference on computer and communications security, 2018), Manticore mitigates overflows, which is of paramount importance for machine learning applications, without compromising efficiency or security. Compared to other overflow-free recent techniques such as MP-SPDZ (Escudero et al., in 40th annual international cryptology conference, CRYPTO. Lecture notes in computer science, 2020) that convert arithmetic to Boolean shares, Manticore uses an efficient modular lifting/truncation method that allows for scalable high numerical precision computations with optimal numerical windows and hence, highly efficient online phases. We adapt basic MPC operations such as real-valued polynomial evaluation, division, logarithms, exponentials, Fourier series evaluations and oblivious comparisons to Manticore by employing our modular lift in combination with existing efficient conversions between arithmetic, Boolean and Yao shares. We also describe a highly scalable computations of logistic regression models with real-world training data sizes and high numerical precision through PCA and blockwise variants (for memory and runtime optimizations) based on second-order optimization techniques. On a dataset of 50 M samples and 50 features distributed among two players, the online phase completes in 14.5 h with at least 10 decimal digits of precision compared to plaintext training. The setup phase of Manticore is supported in both the trusted dealer and the interactive models allowing for tradeoffs between efficiency and stronger security. The highly efficient online phase makes the framework particularly suitable for MPC applications where the output of the setup phase is part of the input of the protocol (such as MPC-in-the-head or Prio). [ABSTRACT FROM AUTHOR]

A central challenge in the study of MPC is to balance between security guarantees, hardness assumptions, and resources required for the protocol. In this work, we study the cost of tolerating adaptive corruptions in MPC protocols under various corruption thresholds. In the strongest setting, we consider adaptive corruptions of an arbitrary number of parties (potentially all) and achieve the following results: (1) A two-round secure function evaluation (SFE) protocol in the CRS model, assuming LWE and indistinguishability obfuscation (iO). The communication, the CRS size, and the online computation are sublinear in the size of the function. The iO assumption can be replaced by secure erasures. Previous results required either the communication or the CRS size to be polynomial in the function size. (2) Under the same assumptions, we construct a “Bob-optimized” 2PC (where Alice talks first, Bob second, and Alice learns the output). That is, the communication complexity and total computation of Bob are sublinear in the function size and in Alice’s input size. We prove impossibility of “Alice-optimized” protocols. (3) Assuming LWE, we bootstrap adaptively secure NIZK arguments to achieve proof size sublinear in the circuit size of the NP relation. On a technical level, our results are based on laconic function evaluation (LFE) (Quach, Wee, and Wichs, FOCS’18) and shed light on an interesting duality between LFE and FHE. Next, we analyze adaptive corruptions of all-but-one of the parties and show a two-round SFE protocol in the threshold-PKI model (where keys of a threshold FHE scheme are pre-shared among the parties) with communication complexity sublinear in the circuit size, assuming LWE and NIZK. Finally, we consider the honest-majority setting and show a two-round SFE protocol with guaranteed output delivery under the same constraints. Our results highlight that the asymptotic cost of adaptive security can be reduced to be comparable to, and in many settings almost match, that of static security, with only a little sacrifice to the concrete round complexity and asymptotic communication complexity. [ABSTRACT FROM AUTHOR]

Secure multi-party computation (MPC) is a fundamental problem in secure distributed computing. An MPC protocol allows a set of n mutually distrusting parties with private inputs to securely compute any publicly known function of their inputs, by keeping their respective inputs as private as possible. While several works in the past have addressed the problem of designing communication-efficient MPC protocols in the synchronous communication setting, not much attention has been paid to the design of efficient MPC protocols in the asynchronous communication setting. In this work, we focus on the design of efficient asynchronous MPC (AMPC) protocol with statistical security, tolerating a computationally unbounded adversary, capable of corrupting up to t parties out of the n parties. The seminal work of Ben-Or, Kelmer and Rabin (PODC 1994) and later Abraham, Dolev and Stern (PODC 2020) showed that the optimal resilience for statistically secure AMPC is t < n / 3 . Unfortunately, the communication complexity of the protocol presented by Ben-Or et al. is significantly high, where the communication complexity per multiplication is Ω (n 13 κ 2 log n) bits (where κ is the statistical-security parameter). To the best of our knowledge, no work has addressed the problem of improving the communication complexity of the protocol of Ben-Or et al. In this work, our main contributions are the following. We present a new statistically secure AMPC protocol with the optimal resilience t < n / 3 , where the communication complexity is O (n 4 κ) bits per multiplication. Apart from improving upon the communication complexity of the protocol of Ben-Or et al., our protocol is relatively simpler and based on very few sub-protocols, unlike the protocol of Ben-Or et al. which involves several layers of sub-protocols. A central component of our AMPC protocol is a new and simple protocol for verifiable asynchronous complete secret-sharing (ACSS), which is of independent interest. As a side result, we give the security proof for our AMPC protocol in the standard universal composability (UC) framework of Canetti (FOCS 2001, JACM 2020), which is now the de facto standard for proving the security of cryptographic protocols. This is unlike the protocol of Ben-Or et al., which was missing the formal security proofs. [ABSTRACT FROM AUTHOR]

In this work, we consider the leakage-resilience of algebraic-geometric (AG for short) codes based ramp secret sharing schemes extending the analysis on the leakage-resilience of linear threshold secret sharing schemes over prime fields that is done by Benhamouda et al. in the effort to construct linear leakage-resilient secret sharing schemes with constant share size. Since there does not exist any explicit efficient construction of AG codes over prime fields with constant field size, we consider constructions over prime fields with the help of concatenation method and constructions of codes over field extensions. Extending the Fourier analysis done by Benhamouda et al., one can show that concatenated algebraic geometric codes over prime fields do produce some nice leakage-resilient secret sharing schemes. One natural and curious question is whether AG codes over extension fields produce better leakage-resilient secret sharing schemes than the construction based on concatenated AG codes. Such construction provides several advantage compared to the construction over prime fields using concatenation method. It is clear that AG codes over extension fields give secret sharing schemes with a smaller reconstruction threshold for a fixed privacy parameter $t$. In this work, it is also confirmed that indeed AG codes over extension fields have stronger leakage-resilience under some reasonable assumptions. Furthermore, we also show that AG codes over extension fields may provide strong multiplicative property which may be used in its application to the study of multiparty computation. In contrast, the same cannot be said for constructions based on concatenated AG codes, even when we are considering multiplication friendly embeddings. These advantages strongly motivate the study of secret sharing schemes from AG codes over extension fields. The current paper has two main contributions: (i) we obtain leakage-resilient secret sharing schemes with constant share sizes and unbounded numbers of players. Some of the schemes constructed without the use of concatenation also possesses strong multiplicative property (ii) via Fourier Analysis, we analyze the leakage-resilience of secret sharing schemes from codes over extension fields. This is of its own theoretical interest independent of its application to secret sharing schemes from algebraic geometric codes over extension fields. [ABSTRACT FROM AUTHOR]

Fully Homomorphic Encryption (FHE) is the holy grail of encrypted communications. It opens the door to several advanced functionalities to overcome the security and trust issues of the IT world. After 2009, once Craig Gentry had shown that FHE could be achieved, a study in this field boomed, and significant improvement was made in identifying more efficient and realistic programs. FHE is primitive cryptography that enables arbitrary functions to be calculated via encrypted data. These systems are applicable in different ways since they permit users to encrypt their private information securely while still outsourcing the processing of protected data without fearing disclosing the real data. In 2012, LTV12 presented the first multi-key FHE system and demonstrated the possibility of using multi-key systems in somewhat homomorphic encryption (SHE). Like in the one key context, there have been many advances in the field, but no effort has been made to develop the multi-key methods. This paper presents a discussion of FHE and MKFHE with a specific focus on the current techniques and three implementations, comprising the first in the multi-key setups, to the extent of our understanding. [ABSTRACT FROM AUTHOR]

The article offers information associated with protein kinase inhibitory nucleosides from the understudied phylum Bryozoa. It is noted that Adenosine triphosphate (ATP) is a critical metabolite employed by human cells to power essential life processes like cell signalling by using energy released by the cleavage of a high-energy phosphate bond.

Kinase inhibitors are a significant and continuously developing division of target therapeutics. The drug discovery and improvement efforts have examined numerous attempts to target the signaling pathway of kinases. The Kinase inhibitors have been heralded as a game-changer in cancer treatment. For developing kinase inhibitors as a treatment for various non-malignant disorders like auto-immune diseases, is currently undergoing extensive research. It may be beneficial to investigate whether cell-specific kinase inhibitor administration enhances therapeutic efficacy and decreases adverse effects. The goal of the current review is to gain insight into the role of kinase inhibitors in facilitating effective target drug delivery for the treatment of various anti-inflammatory, auto-immune, and anticancer disorders. The aim of this review is also to shed light on drug discovery approaches for kinase inhibitors, their mode of action, and delivery approaches. The variation in the binding of kinases bestows different target approaches in drug design, which can be employed for designing the targeted molecules. Several target sites have been studied, exceeding the design of drugs for various diseases like cancer, Alzheimer's, rheumatoid arthritis, etc. Diverse delivery approaches have also been studied for the targeted application of kinase inhibitors. [ABSTRACT FROM AUTHOR]

The serious side effects caused by chemotherapeutics and the development of cancer chemoresistance represent the most significant limitations in the treatment of cancer. Some alternative approaches have been developed in recent years, which are based on natural compounds, and have allowed important advances in cancer therapeutics. During the last 50 years, sponges have been considered a promising source of natural products from the marine environment, representing ~30% of all marine natural products. Among sponges, the Mediterranean species Geodia cydonium represents a potential source of these type of products with considerable biotechnological interest as pharmaceutical agents. The present study demonstrated the antiproliferative effect of an organic G. cydonium extract (GEOCYDO) against three human mesothelioma cell lines, MSTO-211H (MSTO), NCI-H2452 (NCI) and Ist-Mes2 (Mes2), which differ in their sensitivity (MSTO and NCI) and resistance (Mes2) to standard combined treatment with cisplatin and piroxicam. To this aim, the activity of the extract was evaluated by analyzing its effects on cell viability, cancer properties and cell cycle progression by means of colony formation assay, cell cycle analysis and protein expression analysis. The results revealed that in mesothelioma, this extract was able to reduce self-renewal, cell migration and it could induce cell cycle arrest in G0/G1 stage, thus blocking cell proliferation. In conclusion, to the best of our knowledge, the present results indicated for the first time that GEOCYDO can contain active compounds able to affect cell proliferation in mesothelioma, suggesting that it could be considered as a potential novel drug source for cancer treatment. [ABSTRACT FROM AUTHOR]