Numerical Analogue Research Articles

Bakuchiol and their Derivatives: Unveiling its Chemistry, SAR, Pharmacological Marvels and Therapeutic Odyssey

Bakuchiol, a meroterpene natural product found in various plants, exhibits diverse biological activities, notably anticancer properties. Researchers have synthesized numerous analogs targeting different positions, such as alcoholic OH, ethenyl, and isopropylidene groups within bakuchiol, aiming to enlighten potent therapeutic agents with enhanced pharmaceutical characteristics. The review aims to focus on the extensive potential of the bioactive molecule, bakuchiol describing SAR that may lead to the development of a variety of bakuchiol derivatives. Literature survey has been carried out to determine the potential of bakuchiol and its derivatives. This review comprehensively outlines the biosynthesis, isolation, patent, and clinical studies of bakuchiol, and pharmacological potential of bakuchiol derivatives documented to date. Additionally, it explores the structure-activity relationships observed in its derivatives. Collectively, findings from various studies underscore the significant potential of bakuchiol and its derivatives in the development of potent anticancer and other therapeutic agents. Ultimately, this review serves as a valuable resource for researchers interested in both the chemistry and biology of bakuchiol, offering insights into its multifaceted applications and paving the way for further exploration in this field.

Evaluation of Oral Pregabalin as a Preemptive Adjuvant for Postoperative Pain in Patients Undergoing Coronary Artery Bypass Grafting With General Anesthesia and High Thoracic Epidural: A Randomized Controlled Study.

Aim This study aimed to evaluate the effectiveness of oral pregabalin as a preventive supplement in managing postoperative pain in patients undergoing coronary artery bypass grafting (CABG) with a combination of general anesthesia and high thoracic epidural anesthesia. Material and methods This 18-month randomized controlled study at a tertiary hospital's anesthesiology department included 62 American Society of Anesthesiologists (ASA) II or III patients aged 35-75 with left ventricular ejection fraction >35%. Placebo (Group B, n = 31) or pregabalin (Group A, n = 31) was randomly allocated. Group A got 150 mg of pregabalin the night before surgery and 75 mg on postoperative days 0 and 1, whereas Group B received a placebo. Postoperative pain was evaluated using the Verbal Numerical Scale and Visual Analogue Scale, while sedation was assessed with the Ramsay Sedation Scale. Statistical analysis was performed using SPSS for Windows, Version 16.0 (Released 2007; SPSS Inc., Chicago). Results In this study, pregabalin significantly reduced postoperative pain on Day 0 and Day 1 (p < 0.001) compared to the placebo. The pregabalin group exhibited higher sedation scores on Day 0 (p < 0.001), but there were no significant differences on Day 1. Inotrope requirements were similar between both groups. Conclusions CABG patients' postoperative pain was greatly reduced by pregabalin without impacting sedation or inotrope needs. These data imply that pregabalin was a useful supplementary analgesic for CABG patients' multimodal pain treatment.

A novel opioid/pramipexole combination treatment for the management of acute pain: a pilot study.

Despite their dangerous side effects, opioid drugs remain a standard of care for moderate to severe pain with few alternatives. Strategies to maintain the analgesic effects of opioids while minimizing the associated risks are needed. Pre-clinical studies have shown using a dopamine 3 receptor (D3R) agonist as an adjuvant to morphine provides superior analgesia against painful stimuli compared to morphine alone. Our objective was to test if adjunct treatment with a D3R agonist can lead to a reduction in opioid use while maintaining effective analgesia. This study was set up as a double-blinded, placebo-controlled randomized trial. Enrollment included acute renal colic patients presenting to the emergency department, from which patients were randomized to either the "control" or "study arm". The control group received standard treatment of care (morphine, 0.1 mg/kg; i.v.) and an oral placebo pill. The experimental group received half-dosed morphine and oral pramipexole pill (0.25 mg). Pain measurements including a numerical pain scale and visual analog scale were collected from enrollees at baseline and every subsequent 15 min. A total of 19 patients completed the study, 10 in the experimental arm and 9 in the control arm. During the study period, effective analgesia (50% decrease from baseline) was achieved in 80% of patients in the experimental arm vs. 33.3% in the control arm. Our pilot clinical trial demonstrated that D3R recruitment can serve as an effective adjuvant to low-dose morphine for control of renal colic pain and potentially other acute pain conditions. ClinicalTrials.gov, identifier, (NCT04160520).

Newton's cradle: Cell cycle regulation by two mutually inhibitory oscillators

The cell division cycle is a fundamental physiological process displaying a great degree of plasticity during the course of multicellular development. This plasticity is evident in the transition from rapid and stringently-timed divisions of the early embryo to subsequent size-controlled mitotic cycles. Later in development, cells may pause and restart proliferation in response to myriads of internal or external signals, or permanently exit the cell cycle following terminal differentiation or senescence. Beyond this, cells can undergo modified cell division variants, such as endoreplication, which increases their ploidy, or meiosis, which reduces their ploidy. This wealth of behaviours has led to numerous conceptual analogies intended as frameworks for understanding the proliferative program. Here, we aim to unify these mechanisms under one dynamical paradigm. To this end, we take a control theoretical approach to frame the cell cycle as a pair of arrestable and mutually-inhibiting, doubly amplified, negative feedback oscillators controlling chromosome replication and segregation events, respectively. Under appropriate conditions, this framework can reproduce fixed-period oscillations, checkpoint arrests of variable duration, and endocycles. Subsequently, we use phase plane and bifurcation analysis to explain the dynamical basis of these properties. Then, using a physiologically realistic, biochemical model, we show that the very same regulatory structure underpins the diverse functions of the cell cycle control network. We conclude that Newton's cradle may be a suitable mechanical analogy of how the cell cycle is regulated.

The Effect of Foot Reflexology on Fatigue, Sleep Quality, Physiological Indices, and Electrocardiogram Changes in Patients with Acute Myocardial Infarction: A Randomized Clinical Trial.

Limited evidence is available regarding the effect of reflexology on Acute Myocardial Infarction (AMI). The present study evaluated the effect of foot reflexology on fatigue, sleep quality, physiological indices, and electrocardiogram changes in AMI. This clinical trial was conducted on 80 subjects with AMI. They were divided into an intervention (received reflexology for 3 consecutive days) and a control (received the routine care) group. The Multidimensional Fatigue Inventory, the Pittsburgh Sleep Quality Index, a pain numeric analog scale, a daily physiological indices form, and daily electrocardiogram were used to collect data. The collected data were analyzed in SPSS software. The study was conducted based on CONSORT criteria. After controlling the covariates, a significant difference was found between the intervention and control groups with regard to the mean scores of fatigue (F5,80 = 16.33; p < 0.001), sleep quality (F5,80 = 16.56; p < 0.001), and chest pain intensity (F5,80 = 6.86; p = 0.010); means of systolic blood pressure (F5,80 = 22.20; p < 0.001), heart rate (F5,80 = 5.86; p = 0.010), respiration (F5,80 = 9.37; p = 0.003), and temperature (F5,80= -4.23; p < 0.001); and incidence of ST-segment (χ2 1,80 = 5.00; p = 0.020) and T-wave changes (χ2 1,80 = 6.05, p = 0.010) on the fourth day of the intervention. Given the effectiveness of foot reflexology in different aspects of AMI patients, the implementation of this intervention is recommended for these patients in coronary care units.

Pharmacological interventions for pruritus in adult palliative care patients.

Pharmacological interventions for pruritus in adult palliative care patients.

Comparison of laser and traditional lancing devices for capillary blood sampling in patients with diabetes mellitus and high bleeding risk.

Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia. We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared. The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups. The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value.

Molecular docking-based virtual screening and computational investigations of biomolecules (curcumin analogs) as potential lead inhibitors for SARS-CoV-2 papain-like protease

In the effort to combat SARS-CoV-2 infection, researchers are currently exploring the repurposing of conventional antiviral drugs, despite their limited efficacy. The SARS-CoV-2 virus encodes a papain-like protease (PLpro), which not only plays a crucial role in viral replication but also cleaves ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins, making it a prime target for the development of new antiviral medications. In this study, we conducted a multi-step in silico screening to identify novel, noncovalent PLpro inhibitors. Curcumin, an antioxidant derived from turmeric rhizomes (Curcuma longa L.), has undergone extensive preclinical investigations and shown significant efficacy against viruses and other ailments in both laboratory and animal studies. However, the pharmacological limitations of curcumin have prompted the synthesis of numerous novel curcumin analogs, necessitating evaluation for their therapeutic potential. The selectivity of the top-scoring compounds was assessed through molecular docking studies and molecular dynamics simulations to determine their binding affinity to PLpro. As a result, we identified 20 potential, selective PLpro inhibitors, from which the top two compounds (THA111 and THHGV6) were selected based on their binding free energy values towards PLpro as estimated by MM-PBSA calculations. These selected candidates demonstrate promising activity against the protein, with binding free energy values ranging from approximately −105 to −108 kJ/mol, and largely adopt a similar binding mode to known noncovalent SARS-CoV-2PLpro inhibitors (GRL0617 = −100.98 kJ/mol). We further propose these two most promising compounds for future in vitro evaluation. The findings for the top potential PLpro inhibitors have been deposited in a database (Curcumin Research Center) to aid research on anti-SARS-CoV-2 drugs.

Simulation study of compressive mechanical properties of spheroidal cytosolic lattice structures

Ultra-lightweight metallic lattice structures are lightweight functional materials, and the design of their cell elements is a focus of research. Based on the idea of hollow sphere and lattice structure, this paper designs a kind of spherical cytosolic lattice structure, investigates its mechanical properties when compressed by numerical simulation, analyzes its deformation law, derives the nominal stress-strain curve, and investigates the effects of the rod diameter and the cytosolic sphere center distance on the structure’s properties of the effective modulus of elasticity, yield limit, plateau stress, energy absorption and specific energy absorption. The results of the study show that the compressive deformation of the structure exhibits three types depending on the spherical center distance. The mechanical properties of the structure, such as effective modulus of elasticity, yield limit, and plateau stress, show a pattern of decreasing and then increasing with the increase of the spherical center distance, and the minimum value is reached when the spherical center distance is 9.0, but the specific energy absorption of the structure shows a pattern of increasing and then decreasing, and it reaches the maximum value when the spherical center distance is 9.6 mm. The validity of the numerical analog simulation analysis was experimentally verified by 3D printing specimens.

Preoperative subjective assessment of disease-specific quality of life significantly influenced the likelihood of achieving the minimal clinically important difference after surgical stabilization for recurrent lateral patellar instability.

To evaluate which factors exert a predictive value for not reaching the minimal clinically important difference (MCID) in patients who underwent a tailored operative treatment for recurrent lateral patellar dislocation(RLPD). A total of 237 patients (male/female 71/166; 22.4 ± 6.8 years) were included. The Banff Patellofemoral Instability Instrument 2.0 (BPII 2.0) and subjective rating of knee function and pain (numeric analogue scale [NAS]; 0-10) were used to evaluate patients' outcomes from pre- to postoperatively. Gender, age at the time of surgery, body mass index (BMI), nicotine abuse, psychiatric diseases, cartilage statusand pathoanatomic risk factors were evaluated as potential predictors for achieving the MCID using univariate logistic regression analysis. The MCID for the BPII 2.0was calculated at 9.5 points. Although the BPII 2.0 and NAS for knee function and pain improved significantly in the total cohort from pre- to postoperatively (all p < 0.001), 29 patients did not reach the MCID at the final follow-up. The analysis yielded that only the preoperative NAS for function and BPII 2.0 score values were significant predictors for reaching the MCID postoperatively. The optimal threshold was calculated at 7 (NAS function) and 65.2 points (BPII 2.0). Age at the time of surgery should be considered for patients with a preoperative BPII 2.0 score >62.5. The probability of reaching BPII 2.0 MCID postoperatively depends only on the preoperative BPII 2.0 value and subjective rating of knee function, as well as age at the time of surgery for patients undergoing surgical treatment of RLPD. Here, presented results can assist clinicians in advising and presenting patients with potential outcomes following treatment for this often complex and multifactorial pathology. Level III.

Physical pain among family caregivers to older adults: A scoping review of the literature.

Scholarship on the health of family caregivers to older adults continues to expand. Although existing research suggests that many family caregivers experience pain, which impacts their ability to perform caregiving tasks and is associated with care recipients' unmet needs, the scope of research on family caregivers' pain remains poorly characterized. We conducted a scoping review of research on pain among family caregivers to older adults to characterize existing evidence and identify knowledge gaps. We searched multiple databases spanning from January 2012 to July 2023, identified eligible studies using predefined inclusion/exclusion criteria, and extracted key data (e.g., study design/methodology, pain measurement, caregiver pain type, and major findings). We identified 46 eligible studies conducted in the United States (n = 19) and internationally (n = 27). Studies often focused on caregivers for older adults with specific health conditions, such as cancer (n = 11), dementia (n = 8), or stroke (n = 3). The most commonly employed pain measure was a single-item dichotomous question about pain (n = 16), followed by a visual numeric or visual analog scale (n = 11). Nine studies (five randomized controlled trials) reported on five caregiver pain management interventions, including yoga/exercise programs and caregiver education programs. Existing research on family caregivers' pain offers an important foundation. However, more robust research designs are necessary. We identify possibilities for future studies in addition to opportunities for systematic investigations to support the family caregivers being relied upon to care for the increasing number of older adults.

Новые погребальные комплексы сарматского времени из кургана на Кавказских Минеральных Водах

In 2010, the expedition of the Nasledie State Unitary Enterprise (Stavropol) conducted archaeological excavations on the territory of the Caucasian Mineral Waters and excavated the kurgan 1 of the Voniuchka-1 kurgan cemetery near the city of Pyatigorsk. The kurgan originated in the Eneolithic era; its construction and use as a cemetery continued up to the Early and Middle Bronze Ages. The most extensive changes in the kurgan are associated with the North Caucasian archaeological culture. The Sarmatian burials of the early Iron Age became the final ones in the kurgan; this study is devoted to their material publication and analysis. Single burials and grave goods (probably the remains of a funeral feast) were compactly located in the central part of the kurgan. The burial rite and the inventory are described in detail and examined in the system of both chronologically close Sarmatian newcomers and Pre-Caucasus aboriginal monuments. In general, the funeral rite of the published burials is quite uniform and corresponds to the canons of the pre-Caucasian Sarmatian kurgans. The burials and the cluster are chronologically close to each other, and the inventory found in them has numerous analogies among the synchronous sites of the Pre-Caucasus. At the same time, some details of the funeral rite, in particular the discovery of three left front legs of sheep in two burials, together with a number of other facts, indicate a kinship relationship between the buried. The Sarmatian burials in kurgan 1 of the Voniuchka-1 cemetery can be considered a small ancestral cemetery created, most likely, during the lifetime of one generation. The general dating of the burials and the accompanying funeral feast fits into the framework of the 3rd (possibly 2nd) – 1st centuries BC. There is a high probability of their connection with the Sirak tribal union, and this cemetery is located on the southern border of the territory occupied by it.

2-(4-Nitrophenyl)isothiazol-3(2H)-one: A Promising Selective Agent against Hepatocellular Carcinoma Cells.

Liver cancer ranks among the most prevalent malignancies globally and stands as a leading cause of cancer-related mortality. Numerous isothiazolone derivatives and analogues have been synthesized and investigated for their potential as anticancer agents; however, limited data exist regarding their efficacy against liver cancer. In the present study, two nitrophenyl-isothiazolones, the 5-benzoyl-2-(4-nitrophenyl)isothiazol-3(2H)-one (IsoA) and the 2-(4-nitrophenyl)isothiazol-3(2H)-one (IsoB), were preliminarily investigated for their cytotoxicity against hepatoma human (Huh7) cells as a liver cancer model and Immortalized Human Hepatocytes (IHHs) as a model of non-cancerous hepatocytes. IsoB, derived from IsoA after removal of the benzoyl moiety, demonstrated the highest cytotoxic effect against Huh7 cells with CC50 values of 19.3 μΜ at 24 h, 16.4 μΜ at 48 h, and 16.2 μΜ at 72 h of incubation, respectively. IsoB also exhibited selective toxicity against the liver cancerous Huh7 cells compared to IHH cells, reinforcing its role as a potent and selective anticancer agent. Remarkably, the cytotoxicity of IsoB was higher when compared with the standard chemotherapeutical agent 5-fluorouracil (5-FU), which also failed to exhibit higher toxicity against the liver cancerous cell lines. Moreover, IsoB-treated Huh7 cells presented a noteworthy reduction in mitochondrial membrane potential (ΔΨm) after 48 and 72 h, while mitochondrial superoxide levels showed an increase after 24 h of incubation. The molecular mechanism of the IsoB cytotoxic effect was also investigated using RT-qPCR, revealing an apoptosis-mediated cell death along with tumor suppressor TP53 overexpression and key-oncogene MYCN downregulation.

Efficacy of epidural steroid injection in the treatment of sciatica secondary to lumbar disc herniation: a systematic review and meta-analysis.

Epidural steroid injection for the treatment of sciatica caused by disc herniation is increasingly used worldwide, but its effectiveness remains controversial. The review aiming to analyze the efficacy of epidural steroid injection on sciatica caused by lumbar disc herniation. Randomized controlled trials (RCTs) investigating the use of epidural steroid injections in the management of sciatica induced by lumbar disc herniation were collected from PubMed and other databases from January, 2008 to December, 2023, with epidural steroid injection in the test group and epidural local anesthetic and/or placebo in the control group. Pain relief rate, assessed by numerical rating scale (NRS) and visual analogue scale (VAS) scores, and function recovery, evaluated by Roland Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI) scores, were recorded and compared. Meta-analysis was performed by Review Manager. In comparison to the control group, epidural steroid injections have been shown to be effective for providing short- (within 3 months) [MD = 0.44, 95%CI (0.20, 0.68), p = 0.0003] and medium-term (within 6 months) [MD = 0.66, 95%CI (0.09,1.22), p = 0.02] pain relief for sciatica caused by lumbar disc herniation, while its long-term pain-relief effect were limited. However, the administration of epidural steroid injections did not lead to a significant improvement on sciatic nerve function in short- [MD = 0.79, 95%CI = (0.39, 1.98), p = 0.19] and long-term [MD = 0.47, 95% CI = (-0.86, 1.80), p = 0.49] assessed by IOD. Furthermore, the analysis revealed that administering epidural steroid injections resulted in a reduction in opioid usage among patients with lumbar disc herniation [MD = -14.45, 95% CI = (-24.61, -4.29), p = 0.005]. The incidence of epidural steroid injection was low. Epidural steroid injection has demonstrated notable efficacy in relieving sciatica caused by lumbar disc herniation in short to medium-term. Therefore, it is recommended as a viable treatment option for individuals suffering from sciatica.

Spider and Wasp Acylpolyamines: Venom Components and Versatile Pharmacological Leads, Probes, and Insecticidal Agents.

Polyamines (PAs) are polycationic biogenic amines ubiquitously present in all life forms and are involved in molecular signaling and interaction, determining cell fate (e.g., cell proliferation, dif-ferentiation, and apoptosis). The intricate balance in the PAs' levels in the tissues will determine whether beneficial or detrimental effects will affect homeostasis. It's crucial to note that endoge-nous polyamines, like spermine and spermidine, play a pivotal role in our understanding of neu-rological disorders as they interact with membrane receptors and ion channels, modulating neuro-transmission. In spiders and wasps, monoamines (histamine, dopamine, serotonin, tryptamine) and polyamines (spermine, spermidine, acyl polyamines) comprise, with peptides and other sub-stances, the low molecular weight fraction of the venom. Acylpolyamines are venom components exclusively from spiders and a species of solitary wasp, which cause inhibition chiefly of iono-tropic glutamate receptors (AMPA, NMDA, and KA iGluRs) and nicotinic acetylcholine receptors (nAChRs). The first venom acylpolyamines ever discovered (argiopines, Joro and Nephila toxins, and philanthotoxins) have provided templates for the design and synthesis of numerous analogs. Thus far, analogs with high potency exert their effect at nanomolar concentrations, with high se-lectivity toward their ionotropic and ligand receptors. These potent and selective acylpolyamine analogs can serve biomedical purposes and pest control management. The structural modification of acylpolyamine with photolabile and fluorescent groups converted these venom toxins into use-ful molecular probes to discriminate iGluRs and nAchRs in cell populations. In various cases, the linear polyamines, like spermine and spermidine, constituting venom acyl polyamine backbones, have served as cargoes to deliver active molecules via a polyamine uptake system on diseased cells for targeted therapy. In this review, we examined examples of biogenic amines that play an essential role in neural homeostasis and cell signaling, contributing to human health and disease outcomes, which can be present in the venom of arachnids and hymenopterans. With an empha-sis on the spider and wasp venom acylpolyamines, we focused on the origin, structure, derivatiza-tion, and biomedical and biotechnological application of these pharmacologically attractive, chemically modular venom components.

A combined in vitro-in silico method for assessing the androgenic activities of bisphenol A and its analogues

Interactions between endocrine-disruptor chemicals (EDCs) and androgen receptor (AR) have adverse effects on the endocrine system, leading to human reproductive dysfunction. Bisphenol A (BPA) is an EDC that can damage both the environment and human health. Although numerous BPA analogues have been produced as substitutes for BPA, few studies have evaluated their endocrine-disrupting abilities. We assessed the (anti)-androgenic activities of BPA and its analogues using a yeast-based reporter assay. The BPA analogues tested were bisphenol S (BPS), 4-phenylphenol (4PP), 4,4′-(9-fluorenyliden)-diphenol (BPFL), tetramethyl bisphenol F (TMBPF), and tetramethyl bisphenol A (TMBPA). We also conducted molecular docking and dynamics simulations to assess the interactions of BPA and its analogues with the ligand-binding domain of human AR (AR-LBD). Neither BPA nor its analogues had androgenic activity; however, all except BPFL exerted robust anti-androgenic effects. Consistent with the in vitro results, anti-androgenic analogues of BPA formed hydrogen bonding patterns with key residues that differed from the patterns of endogenous hormones, indicating that the analogues display in inappropriate orientations when interacting with the binding pocket of AR-LBD. Our findings indicate that BPA and its analogues disrupt androgen signaling by interacting with the AR-LBD. Overall, BPA and its analogues display endocrine-disrupting activity, which is mediated by AR.

Rikkosan's Short-Term Analgesic Effect on Burning Mouth Syndrome: A Single-Arm Cohort Study.

Burning mouth syndrome (BMS) is a chronic oral pain disorder. There is a theory that BMS is a form of nociplastic pain. A standard treatment for BMS has not yet been established. Kampo medicine is a traditional oriental medicine. The purpose of this study is to evaluate the effectiveness of Rikkosan-a traditional Japanese herbal medicine (Kampo)-in the treatment of BMS. A single-center retrospective study was conducted on 20 patients who were diagnosed with BMS and treated with Rikkosan alone (total daily dose; 7.5 g) three times daily for approximately 4 weeks (29.5 ± 6.5 days). Rikkosan was dissolved in hot water and taken internally. They had an average age of 63 years, and 90% were being treated for other illnesses, but their medication status was the same during this study period, except for Rikkosan. No adverse events were observed in patients. Numerical rating scale (NRS) or visual analog scale (VAS)/10 scores decreased significantly between the time of the initiation of Rikkosan and one month after (-2.1 ± 1.2, p < 0.05). Rikkosan has a short-term effect of reducing NRS by two levels in BMS patients.

Exploring Synthesis and Medicinal Applications of Andrographolide Derivatives: A Review

Abstract: Andrographolide, derived from the plant Andrographis paniculata (AP), exhibits a diverse range of biological activities, encompassing anti-bacterial, anti-tumor, antiinflammatory, anti-obesity, anti-viral, anti-fibrotic, hypoglycemic, and immunomodulatory properties. Notably, numerous analogues of andrographolide have been synthesized, incorporating significant chemical structural modifications to enhance bioavailability and druggability. A comprehensive exploration into their molecular and cellular mechanisms of action has also been undertaken, enriching our understanding. The investigation highlights the potential of related terpenoid analogues from Andrographis paniculata, beyond the diterpene lactone andrographolide, to hold promise in disease treatment due to structural similarities and diverse pharmacological effects. This review offers insights into the anticipated synthesis and therapeutic applications of andrographolide derivatives across a spectrum of disorders.

Post-COVID-19 Rhino-Orbito-Maxillary Mucormycosis Defect: Our Surgical Experience with Single Stage Delayed Reconstruction Using Free Flap

Abstract Introduction The effect of the second wave of COVID-19 was immense in India, specifically in the form of vicious COVID-19-associated mucormycosis. A higher number of radical debridements are required for disease control in combination with antifungal drugs in cases of COVID-19-associated mucormycosis, which results in complex maxillofacial defects. We aimed to evaluate the clinical outcomes in patients with rhino-orbito-maxillary defects due to COVID-19-associated mucormycosis undergoing a single stage delayed free flap reconstruction. Methodology This prospective, single-center, multisurgeon study was performed on eight patients with COVID-19-associated rhino-orbito-maxillary mucormycosis in the department of burns and plastic surgery. The postoperative clinical outcome was evaluated using the University of Washington Quality of Life Questionnaire for patient's quality of life (QOL), aesthetic numeric analog (ANA) scale for patient's satisfaction for aesthetics, and the functional intraoral Glasgow scale for speech and deglutition at 1 and 3 months. Results The median age of the study patients was 40 years, with 75% of the patients being males. Diabetes mellitus (DM) was present in all the patients. Mucormycosis was diagnosed within the first 3 months of COVID-19 infection. Maxillary defect was present in 62.5% of patients, out of which 50% had bilateral maxillary defects. There was significant improvement in the QOL and the aesthetics of patients from 1 to 3 months (p &lt; 0.001). Speech and deglutition were also improved at 3 months, but the difference was not statistically significant. Conclusion Single stage delayed free flap reconstruction can be advocated in patients with COVID-19-associated rhino-orbito-maxillary mucormycosis defect as there is considerable improvement in patients' QOL, aesthetics, speech, and deglutition over a period of time.

Long head of biceps tendon augmentation for massive rotator cuff tears improves clinical results regardless of the number of tendons involved.

Management of massive rotator cuff tears (MRCTs) remains debated, and various arthroscopic and open techniques have been described for their management. Nevertheless, the optimal strategy remains unclear. The present study evaluated the clinical results in patients managed arthroscopically for MRCTs augmented with the long head biceps tendon (LHBT) at a minimum 1-year follow-up, considering different type of tears, demographic data and number of torn tendons. Patients treated in a secondary referral centre from January 2021 to April 2022 were enroled prospectively. Inclusion criteria were pain, inability to fully elevate the affected shoulder, irreparable tears and active and motivated patients. All patients were managed within 2 months from diagnosis in a single centre by the same surgeons. Preoperative shoulder radiographs and magnetic resonance imaging (MRI) were collected, and clinical assessment was also performed using the Numerical analogue scale (NAS), Constant score (CS) American Shoulder and Elbow Surgeons Shoulder Score (ASES). Tissue retraction and tendon fatty infiltration were evaluated using Patte and Fuchs scale, respectively. Clinical assessment was performed using the same scales at 3-6 months and 1-year follow-up. A total of 55 patients (31 female and 24 male) with a mean age of 60 ± 7.1 years were enroled for a mean follow-up of 18.2 ± 4.3 months. The mean preoperative NAS was 7.8 ± 0.6, CS was 20.5 ± 7.6 and ASES was 22.6 ± 9.2, increasing, respectively, to 0.3 ± 0.6, 91.5 ± 6.9 and 94.2 ± 6.7. No adverse side effects (infection, rejection, allergy) were reported during the study period. All patients were evaluated after surgery at 3 and 6 months and 1 year with statistically significant improvement for each score at the first and last follow-up (p < 0.05). The use of LHBT augmentation in patients with MRCTs in appropriately selected patients is safe and effective and can lead to pain relief and acceptable clinical outcomes. Furthermore, its use carries low donor site morbidityand is cost effective. Comparative studies, including randomised controlled trials, with other proposed techniques are needed to confirm these findings. Level IV.