Acid Therapy Research Articles

Treatment of acute pharyngitis in children: an Italian intersociety consensus (SIPPS-SIP-SITIP-FIMP-SIAIP-SIMRI-FIMMG).

Sore throat represents one of the main causes of antibiotic overprescription in children. Its management is still a matter of debate, with countries considering streptococcal pharyngotonsillitis a benign and self-limiting condition and others advocating for its antibiotic treatment to prevent suppurative complications and acute rheumatic fever. Italian paediatricians frequently prescribe antibiotics on a clinical basis regardless of microbiological results. Moreover, broad-spectrum antibiotics are inappropriately prescribed for this condition. In this regard, an intersociety consensus conference was issued to promote the judicious use of antibiotic therapy in paediatric outpatient settings. A systematic review of the literature was performed, and updated recommendations were developed according to the GRADE methodology. Antibiotic treatment with amoxicillin (50mg/kg/day) for 10 days is recommended in all children with proven streptococcal pharyngitis. Benzathine-penicillin could be prescribed in children with impaired intestinal absorption or inability to tolerate enteral intake and in those at high risk of suppurative complications with low compliance to oral therapy. In children with suspected amoxicillin allergy, third-generation cefalosporins for five days are recommended in low-risk patients, and macrolides are recommended in high-risk ones. Candidates for tonsillectomy due to recurrent pharyngitis could be treated with amoxicillin-clavulanic acid, clindamycin, or combined therapy with amoxicillin plus rifampicin for four days, in an attempt to avoid surgery.

The Effect of Adjuvant Therapy on Metabolic Syndrome in Schizophrenia Patients at Madani Hospital

Background: Schizophrenia is a mental disorder that impacts behavior, emotions, and communication. In recent years, atypical antipsychotics have been increasingly prescribed because they significantly reduce both positive and negative symptoms. However, the long-term effects of atypical can cause metabolic syndrome. Additional therapy is provided to maximize the primary therapy and reduce the side effects. Method: This study used a quasi-experimental design with a single-blind, pretest-posttest approach. Patients who had been using atypical antipsychotics, either monotherapy or combination therapy, for more than 3 were examined pretest to determine metabolic syndrome levels. Group A received adjuvant therapy, while Group B did not receive adjuvant therapy. Based on this data, an analysis of the reduction in metabolic syndrome categories was conducted. Result: The percentage of schizophrenia patients by gender was dominated by males (60%). By age, the majority were adults (87%). In Group A, the incidence of metabolic syndrome decreased from 53% in the pretest to 40% in the posttest after being given vitamin A, B, and folic acid therapy. The most commonly used other medication was THP (38%). Conclusion: The administration of adjuvant therapy with vitamins A, B, E, and folic acid can reduce the value of one or two of the five metabolic syndrome criteria for schizophrenia patients (p = 0.052) compared to the group of patients who did not receive vitamins A, B, E, and folic acid adjuvant therapy. Future research should use a longer duration to observe the effects of vitamins A, B, E, and folic acid and evaluate their therapeutic doses. Additionally, it should narrow down the criteria for medication use, focusing solely on the atypical antipsychotic’s clozapine or olanzapine.

Middle meningeal artery embolization and tranexamic acid therapy for subdural hematoma in a patient with hereditary hemorrhagic telangiectasia: illustrative case.

Subdural hematoma is a rare manifestation of hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease. Here, the authors present a patient with HHT and a large chronic subdural hematoma, for whom nonsurgical management was pursued. A 49-year-old right-handed male with a history of hypertension and familial HHT presented with complaints of mild confusion and left hemiparesis over several days. Noncontrast head computed tomography images demonstrated a large chronic right hemisphere subdural hematoma compressing the right cerebral hemisphere and causing a 1.3-cm midline shift. Due to concerns about surgical complications arising from hemorrhages of cryptic telangiectasias, the patient was treated conservatively with middle meningeal artery embolization and adjuvant tranexamic acid. There was clinical and radiological resolution several months later. This case highlights the rarity of a subdural hematoma as a manifestation of HHT and the nonsurgical treatment strategy as a mechanism to avoid hemorrhagic complications of surgical evacuation. https://thejns.org/doi/10.3171/CASE24483.

Ultrasound-guided interventions in elite soccer players.

In the world of elite soccer, or football as we call it in the UK, a player who cannot play for any length of time costs the team money and team performance. The time to return to play (RTP) is crucial in any player's career, and the use of ultrasound-guided ultrasound injections has become important in the management of injury. In this article, I will explain the importance of good practice when performing these procedures and the use of steroids, sodium hyaluronic acid, platelet-rich plasma (PRP), and other therapies in achieving the goal of decreasing the time of RTP for the footballer. KEY POINTS: •Injection therapies are routine practice in maintaining and treating soccer injuries. •Injection therapies can be safely performed under ultrasound guidance.

Foreign-body granuloma formation in the lower eyelid after injection of poly-D,L-lactic acid as a collagen stimulator: a case report

Poly-D,L-lactic acid (PDLLA) is widely used in facial rejuvenation as a collagen stimulator, with a lower risk of granuloma formation compared to poly-L-lactic acid (PLLA). However, granulomas may still occur. In this case, a 58-year-old woman developed firm, non-tender, bilateral infraorbital granulomas 2 months after her third PDLLA injection for infraorbital hollowing. The lesions were unresponsive to intralesional trichloroacetic acid (TCA) and intense pulsed light therapy, necessitating surgical removal. Histopathological analysis confirmed foreign-body granulomas caused by the PDLLA filler. This case highlights the need for caution when injecting PDLLA into thin-skinned areas like the infraorbital region, where granulomas can be more visible due to limited tissue volume. Although PDLLA fillers are generally safe, granuloma formation remains a potential complication. Early diagnosis and treatment with non-surgical methods, such as intralesional TCA, should be prioritized. If these methods fail, surgical excision, aimed at preserving as much normal tissue as possible, may be necessary for optimal outcomes.

Osteoporosis in Systemic Mastocytosis: A Scoping Review

Background: Mastocytosis (MS) is a rare disease that can involve various organs, including the bone. Given the incidence of the disease in the global population, MS poses a challenge for physicians, and early therapeutic intervention in the initial stages could significantly impact the quality of life of affected patients. Objective: The aim of this scoping review was to provide an overview of secondary osteoporosis in systemic mastocytosis (SM), focusing on the heterogeneity of its manifestations, the benefits of early diagnosis, and appropriate pharmacological treatment. Design: A technical expert panel (TEP) consisting of 8 physicians with expertise in metabolic bone diseases conducted the review following the PRISMA-ScR model. A strength of this study is that it provides various therapeutic approaches for patients with bone involvement in SM, although the limited available literature on the topic constituted a limitation. The TEP sought evidence regarding the following diagnostic and therapeutic modalities in the management of SM: “bisphosphonate therapy”, “zoledronic acid therapy”, “denosumab therapy”, “IFN-alpha therapy”, and “IFN-alpha therapy in combination with pamidronate”. Results: Clinical data showed a correlation between densitometric outcomes, serum tryptase levels, and mast cell infiltration in the bone marrow, between increased bone mineral density and the presence of osteosclerosis in cases of advanced SM, between the severity of osteoporosis and hypertryptasemia, and also provided results on the long-term effects of bisphosphonate therapy, the therapeutic efficacy of zoledronic acid administration, the positive effect of denosumab on the reduction of serum tryptase levels (even if is proved in a limited numbers of cases) and the prevention of new fractures, and the effect of IFN-alpha in more severe cases of SM, either alone or in combination with pamidronate. Conclusions: Studies have demonstrated the effectiveness of various treatments depending on the form of mastocytosis, whether indolent systemic or advanced systemic, in the prognosis of the disease. However, this role should be further investigated in additional clinical studies, considering the limited data on the use of these interventions.

Spleen Targeting Nucleic Acid Delivery Vector Based on Metal-Organic Frameworks.

Nucleic acids have attracted increasing attention as drugs due to their fascinating advantages, such as long-term efficacy and ease of preparation compared to proteins. The nucleic acid therapy relies heavily on delivery vectors, which can prevent the degradation of nucleic acids while assisting them in cellular internalization. However, commonly used nonviral vector liposomes easily accumulate in the liver, which can limit their application in extrahepatic diseases. Herein, a potential spleen targeting vector for nucleic acids is developed based on the metal-organic frameworks. The plasmids are encapsulated inside the nanoscale zeolitic imidazolate framework (ZIF) via coprecipitation. The co-encapsulation of the cationic polymer poly(ether imide) (PEI) and the stabilizer polyvinylpyrrolidone (PVP) can significantly improve particle dispersion and stability. The prepared nanoparticles allow efficient transfection in vitro, mainly through clathrin-mediated and caveolae-mediated endocytosis. The biodistribution in mice shows that 46% of the nanoparticles accumulate in the spleen, which is much higher than that of the liposomes. The vector can successfully deliver plasmids to extrahepatic organs for protein synthesis and even induce an immune response. The elaborate ZIF-based nanoparticle may offer a new route for extrahepatic, especially spleen targeting delivery for the nucleic acids.

High-dose IV ascorbic acid therapy for patients with CCUS with TET2 mutations

AbstractThis was a phase 2 trial evaluating the safety/efficacy of high-dose IV ascorbic acid in patients with TET2 mutant clonal cytopenia(s) of undetermined significance. Eight of 10 patients enrolled were eligible for response assessment. At week 20, there were no responses by International Working Group MDS criteria. The trial was registered at www.clinicaltrials.gov as #NCT03418038.

Recent Advances and Prospects of Nucleic Acid Therapeutics for Anti-Cancer Therapy

Nucleic acid therapeutics are promising alternatives to conventional anti-cancer therapy, such as chemotherapy and radiation therapy. While conventional therapies have limitations, such as high side effects, low specificity, and drug resistance, nucleic acid therapeutics work at the gene level to eliminate the cause of the disease. Nucleic acid therapeutics treat diseases in various forms and using different mechanisms, including plasmid DNA (pDNA), small interfering RNA (siRNA), anti-microRNA (anti-miR), microRNA mimics (miRNA mimic), messenger RNA (mRNA), aptamer, catalytic nucleic acid (CNA), and CRISPR cas9 guide RNA (gRNA). In addition, nucleic acids have many advantages as nanomaterials, such as high biocompatibility, design flexibility, low immunogenicity, small size, relatively low price, and easy functionalization. Nucleic acid therapeutics can have a high therapeutic effect by being used in combination with various nucleic acid nanostructures, inorganic nanoparticles, lipid nanoparticles (LNPs), etc. to overcome low physiological stability and cell internalization efficiency. The field of nucleic acid therapeutics has advanced remarkably in recent decades, and as more and more nucleic acid therapeutics have been approved, they have already demonstrated their potential to treat diseases, including cancer. This review paper introduces the current status and recent advances in nucleic acid therapy for anti-cancer treatment and discusses the tasks and prospects ahead.

Analysis of bleeding outcomes in patients with hypoproliferative thrombocytopenia in the A-TREAT clinical trial.

Despite prophylactic platelet transfusions, hypoproliferative thrombocytopenia is associated with bleeding; historical risk factors include hematocrit (HCT) 25%, activated partial thromboplastin time 30 s, international normalized ratio 1.2, and platelets 5000/μL. We performed a post hoc analysis of bleeding outcomes and risk factors in participants with hematologic malignancy and hypoproliferative thrombocytopenia enrolled in the American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A-TREAT) and randomized to receive either tranexamic acid (TXA) or placebo. World Health Organization (WHO) grade 2+ bleeding occurred in 46% of 330 participants, with no difference between the TXA (44%) and placebo (47%) groups (p = 0.66). Overall, the most common sites of bleeding were oronasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%). Among participants of childbearing potential, 28% experienced vaginal bleeding. Platelets ≤5000/μL and HCT < 21% (after adjusting for severe thrombocytopenia) were independently associated with increased bleeding risk (HR 3.78, 95% CI 2.16-6.61; HR 2.67, 95% CI 1.35-5.27, respectively). Allogeneic stem cell transplant was associated with nonsignificant increased risk of bleeding versus chemotherapy alone (HR 1.34, 95% CI 0.94-1.91). The overall rate of WHO grade 2+ bleeding was similar to previous reports, albeit with lower rates of gastrointestinal bleeding. Vaginal bleeding was common in participants of childbearing potential. Platelets ≤5000/μL remained a risk factor for bleeding. Regardless of platelet count, bleeding risk increased with HCT < 21%, suggesting a red blood cell transfusion threshold above 21% should be considered to mitigate bleeding. More investigation is needed on strategies to reduce bleeding in this population.

Novel sodium tauroursodeoxycholate-based multifunctional liposomal delivery system for encapsulation of oleanolic acid and combination therapy of type 2 diabetes mellitus

Liposomes have demonstrated great potential for drug delivery and diabetes treatment. However, hydrolysis by enzymes and emulsification by endogenous bile salts make liposomes unstable in the gastrointestinal tract. In this study, sodium tauroursodeoxycholate (TUDCNa)-based multifunctional bilosomes were designed to address the deficiencies of conventional liposomes. In the designed bilosomes, cholesterol was replaced by TUDCNa, which served as both a membrane stabilizer and an antidiabetic drug. Oleanolic acid (OA) was encapsulated in both conventional liposomes (OA-Ch-Lip) and bilosomes (OA-Tu-Bil) to compare their properties. Firstly, OA-Tu-Bil exhibited similar encapsulation efficiency and drug loading compared to OA-Ch-Lip, but with a smaller particle size. Secondly, OA-Tu-Bil showed better stability than OA-Ch-Lip. Thirdly, bilosomes exhibited prolonged intestinal retention time and improved permeability and oral bioavailability. Fourthly, in type 2 diabetes mellitus (T2DM) mice model, TUDCNa synergized with OA to exhibit the strongest therapeutic effect. In conclusion, TUDCNa have demonstrated the ability to substitute cholesterol in conventional liposomes, it provided a new approach for oral delivery of hypoglycemic drugs, and offered an innovative strategy for combination therapy.

Dermatologic Procedures for the Treatment of Seborrheic Dermatitis.

This paper examines alternative procedural interventions for Seborrheic Dermatitis (SD), aiming to offer clinicians more treatment options and encourage further research. A search was conducted on PubMed using specific search terms related to SD and various dermatological procedures. Studies in English, focusing on SD in human patients, and in-office treatments were included. Data were analyzed for procedure type, effectiveness, and side effects. Nine studies were reviewed, covering phototherapy, indole-3-acetic acid photodynamic therapy (IAA-PDT), Picosecond Nd:YAG laser, botulinum toxin (BoNT) injections, triamcinolone injections, hair growth factor therapy, and precision cryotherapy. Most showed significant efficacy in small cohorts with high patient satisfaction. Hair growth factor therapy had long-term benefits, while narrow-band ultraviolet B phototherapy showed relapse within one month. Intense pulsed light with supramolecular salicylic acid, IAA-PDT, and laser therapy reduced sebum output and Malassezia furfur. Triamcinolone injections were effective against SD's immunological aspects. Hair growth factor therapy and precision cryotherapy have been successfully used to treat scalp SD. The role of BoNT in SD is still being explored; however, current evidence does not support its use. Limited data reveal the need for further research on dermatological procedures for SD. These methods show promise for better patient compliance but face challenges such as cost, variable effectiveness, and unknown long-term safety. Future research should focus on protocol standardization and comprehensive evaluation of long-term outcomes. J Drugs Dermatol. 2024;23(10):819-824. doi:10.36849/JDD.8116.

Vaginal Natural Oxygenation Device (VNOD) and Lichen: A Pilot Study on the Assessment of Effectiveness of the Simultaneous and Local Administration of High Concentration Oxygen and Hyaluronic Acid to treat Vulvar Lichen Scleroatrophicus

Background This is a pilot study to assess the effectiveness of simultaneous and local administration of high concentration oxygen and hyaluronic acid by a specific medical device (VNOD) to improve vulvar lichen symptoms healing vulvar lesions. Methods 17 women with histological diagnosis of vulvar lichen were included. Five weekly administrations of concomitant oxygen-hyaluronic acid therapy with VNOD were performed. The severity of the pathology was evaluated using the Vaginal Health Index (VHI). Patients’ symptoms were evaluated with two questionnaires: VAS and FSFI. VAS, FSFI and VHI were evaluated at the start and at the end of the therapy. The statistical analysis was performed according to the Kruskal-Wallis method and using the t-test calculator. Results The study has showed that each subsequent treatment determined a significant increase in all parameters, especially for VHI hydration index, VAS fluidity index and FSFI lubrication index, however all the patients reported a recovery of their sexuality at the end of the five treatment sessions. All the parameters maintain their value at six weeks of follow-up. No adverse effects were observed. Conclusions Combined topical oxygen therapy with hyaluronic acid by VNOD seems to be a valid and totally painless treatment for vulvar lichen scleroatrophicus, improving symptomatology, and sexual wellbeing.

Acetylsalicylic acid and dihydroartemisinin combined therapy on experimental malaria-associated acute lung injury: analysis of lung function and the inflammatory process

BackgroundSevere malaria can cause respiratory symptoms, which may lead to malaria-acute lung injury (MA-ALI) due to inflammation and damage to the blood-gas barrier. Patients with severe malaria also often present thrombocytopenia, and the use of acetylsalicylic acid (ASA), a commonly used non-steroidal anti-inflammatory drug with immunomodulatory and antiplatelet effects, may pose a risk in regions where malaria is endemic. Thus, this study aimed to investigate the systemic impact of ASA and dihydroartemisinin (DHA) on ALI induced in mice by Plasmodium berghei NK65 (PbNK65).MethodsC57BL/6 mice were randomly divided into control (C) and PbNK65 infected groups and were inoculated with uninfected or 104 infected erythrocytes, respectively. Then, the animals were treated with DHA (3 mg/kg) or vehicle (DMSO) at the 8-day post-infection (dpi) for 7 days and with ASA (100 mg/kg, single dose), and analyses were performed at 9 or 15 dpi. Lung mechanics were performed, and lungs were collected for oedema evaluation and histological analyses.ResultsPbNK65 infection led to lung oedema, as well as increased lung static elastance (Est, L), resistive (ΔP1, L) and viscoelastic (ΔP2, L) pressures, percentage of mononuclear cells, inflammatory infiltrate, hemorrhage, alveolar oedema, and alveolar thickening septum at 9 dpi. Mice that received DHA or DHA + ASA had an increase in Est, L, and CD36 expression on inflammatory monocytes and higher protein content on bronchoalveolar fluid (BALF). However, only the DHA-treated group presented a percentage of inflammatory monocytes similar to the control group and a decrease in ΔP1, L and ΔP2, L compared to Pb + DMSO. Also, combined treatment with DHA + ASA led to an impairment in diffuse alveolar damage score and lung function at 9 dpi.ConclusionsTherapy with ASA maintained lung morpho-functional impairment triggered by PbNK65 infection, leading to a large influx of inflammatory monocytes to the lung tissue. Based on its deleterious effects in experimental MA-ALI, ASA administration or its treatment maintenance might be carefully reconsidered and further investigated in human malaria cases.

Predictors of Clinical Benefit with Intra-articular Hyaluronic Acid in Patients with Knee Osteoarthritis - A Narrative Review.

There is conflicting evidence regarding the efficacy of viscosupplementation with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit from this therapy. The purpose of this narrative review is to succinctly summarize the existing data on the predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile most likely to benefit from this therapy. For this narrative review, a PubMed search was conducted in January 2023, with no date limits, to identify publications reporting predictive factors of response to viscosupplementation using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta- analyses, or observational studies written in English. Other relevant references were identified by searching the references of retrieved articles. The disease severity was found to reliably predict response to intra-articular hyaluronic acid injections; patients with less severe disease consistently had a more robust therapeutic response than those with more severe disease. Other clinical variables such as level of baseline pain did not reliably predict response. Body mass index, and possibly age, may also be independent predictors of the response. A review of the existing literature suggests that patients with less severe clinical symptoms and radiological findings, who are younger, and with a lower or normal body mass index are the best candidates for intra-articular hyaluronic acid therapy.

Established and Emerging Nucleic Acid Therapies for Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is a genetic disease that leads to elevated low-density lipoprotein cholesterol levels and risk of coronary heart disease. Current therapeutic options for FH remain relatively limited and only partially effective in both lowering low-density lipoprotein cholesterol and modifying coronary heart disease risk. The unique characteristics of nucleic acid therapies to target the underlying cause of the disease can offer solutions unachievable with conventional medications. DNA- and RNA-based therapeutics have the potential to transform the care of patients with FH. Recent advances are overcoming obstacles to clinical translation of nucleic acid-based medications, including greater stability of the formulations as well as site-specific delivery, making gene-based therapy for FH an alternative approach for treatment of FH.

Systematic Review of Genetic Substrate Reduction Therapy in Lysosomal Storage Diseases: Opportunities, Challenges and Delivery Systems.

Genetic substrate reduction therapy (gSRT), which involves the use of nucleic acids to downregulate the genes involved in the biosynthesis of storage substances, has been investigated in the treatment of lysosomal storage diseases (LSDs). To analyze the application of gSRT to the treatment of LSDs, identifying the silencing tools and delivery systems used, and the main challenges for its development and clinical translation, highlighting the contribution of nanotechnology to overcome them. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines was performed. PubMed, Scopus, and Web of Science databases were used for searching terms related to LSDs and gene-silencing strategies and tools. Fabry, Gaucher, and Pompe diseases and mucopolysaccharidoses I and III are the only LSDs for which gSRT has been studied, siRNA and lipid nanoparticles being the silencing strategy and the delivery system most frequently employed, respectively. Only inone recently published studywas CRISPR/Cas9 applied to treatFabry disease. Specific tissue targeting, availability of relevantcell and animal LSD models, and the rare disease condition are the main challenges with gSRT for the treatment of these diseases. Out of the 11 studies identified, only two gSRT studies were evaluated in animal models. Nucleic acid therapies are expanding the clinical tools and therapies currently available for LSDs. Recent advances in CRISPR/Cas9 technology and the growing impact of nanotechnology are expected to boost the clinical translation of gSRT in the near future, and not only for LSDs.

Illuminating the fight against breast cancer: Preparation and visualized photothermal therapy of hyaluronic acid coated ZIF-8 loading with indocyanine green and cryptotanshinone for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is characterized by higher recurrence rate and mortality. Thermally-mediated ablation via photothermal therapy (PTT) demonstrates considerable promise for the eradication of breast cancer. Nonetheless, the efficacy of PTT is impeded by the thermal tolerance of tumor cells, which is attributed to the augmented expression of heat shock proteins (HSPs). These proteins, which function as ATP-dependent molecular chaperones, confer protection to cancer cells against the cytotoxic heat generated during PTT. Glycolysis is an important way for breast cancer cells to produce ATP, which can promote the occurrence and development of lung metastasis of breast cancer. Therefore, inhibiting glycolysis may diminish the expression of HSPs, curtail the growth of breast cancer, and prevent its metastasis. Glycolytic metabolism plays a pivotal role in the ATP biosynthesis within breast cancer cells, facilitating the progression and dissemination of pulmonary metastases. Consequently, targeting glycolysis presents a strategic approach to HSP expression, the proliferation of breast cancer, and impede its metastatic spread. Herein, we designed an indocyanine green (ICG) and cryptotanshinone (CTS) loaded hyaluronic acid (HA) coated Zeolitic Imidazolate Framework-8 (ZIF-8) drug delivery system. The drug delivery system had excellent photothermal properties, which could reach temperature sufficient for photothermal ablation of tumor cells. (ICG + CTS)@HA-ZIF-8 also showed pH-responsive drug release, enhancing the sustained release of ICG and CTS to extend their systemic circulation duration. Moreover, the HA modification of ZIF-8 served to augment its targeting capabilities both in vitro and in vivo, leveraging the enhanced permeation and retention (EPR) effect, as well as active tumor targeting via the CD44 receptor pathway, resulting in a higher drug concentration and a better therapeutic effect in tumor. (ICG + CTS)@HA-ZIF-8 could downregulate the expression of glycolysis-related protein pyruvate kinase-M2 (PKM2), thereby inhibiting the glycolysis process, further suppressing tumor cell energy metabolism, downregulating the expression of HSPs, overcoming tumor cell heat resistance, and improving PTT effect. It exhibited a notable suppressive impact on both the proliferation and migration of breast cancer cells, potentially offering innovative insights for the visualized PTT in breast cancer treatment.

Papain-Mediated Conjugation of Peptide Nucleic Acids to Delivery Peptides: A Density Functional Theory/Molecular Mechanics Metadynamics Study in Aqueous and Organic Solvent.

Enzymatic peptide synthesis is a powerful alternative to solid-phase methods, as enzymes can have high regio- and stereoselectivity and high yield and require mild reaction conditions. This is beneficial in formulation research due to the rise of nucleic acid therapies. Peptide nucleic acids (PNAs) have a high affinity toward DNA and RNA, and their solubility and cellular delivery can be improved via conjugation to peptides. Here, we designed and assessed the viability of the papain enzyme to conjugate four PNA-peptide models in water and an organic solvent using QM/MM metadynamics. We found that the reactions in water yield better results, where three conjugates could potentially be synthesized by the enzyme, with the first transition state as the rate-limiting step, with an associated energy of 14.53 kcal mol-1, although with a slight endergonic profile. The results highlight the importance of considering the enzyme pockets and different substrate acceptivities and contribute to developing greener, direct, and precise synthetic routes for nucleic acid-based therapies. By exploring the enzyme's potential in conjunction with chemical synthesis, current protocols can be simplified for the synthesis of longer nucleic acids and peptide sequences (and, by extension, proteins) from smaller oligo or peptide blocks.

A cross-sectional study on factors associated with iron-folic acid supplement adherence among antenatal women of Haringhata block of Nadia district, West Bengal

Background: Anaemia, lack of can cause health complications across all age groups, particularly among pregnant women. In India, despite various governmental and non-governmental initiatives, the coverage and compliance of iron folic acid (IFA) therapy among pregnant women remain inadequate. This study aimed to estimate the prevalence of non-adherence and its determinants among pregnant mothers in Haringhata block, Nadia district, West Bengal. Methods: A community-based cross-sectional study was conducted, selecting eligible pregnant mothers through simple random sampling from sub-centre lists. Confidential interviews were conducted using a pre-designed, structured questionnaire, with informed consent obtained from participants. Data were entered in Microsoft excel and analyzed using statistical package for the social sciences (SPSS) 20.0. Results: Results showed that 37.7% of pregnant women were anaemic, and 19.9% were non-adherent to IFA supplements. Among the non-adherent, 56.5% missed IFA intake due to forgetfulness. Lack of knowledge was a significant barrier, with 53.42% unaware of IFA benefits and none knowing the exact duration of intake. Bivariate analyses indicated higher odds of non-adherence among mothers whose husbands were unemployed/unskilled, who suffered from anaemia, and who lacked knowledge about IFA benefits. Conclusions: The study findings suggest that addressing forgetfulness, providing accurate knowledge about IFA intake, and targeted interventions for teenage mothers can improve adherence rates, preventing anaemia and enhancing maternal and child health outcomes.