Unraveling the spatio-temporal dynamics of soil and root-associated microbiomes in Texas olive orchards.

Understanding the structure and diversity of microbiomes is critical to establishing olives in non-traditional production areas. Limited studies have investigated soil and root-associated microbiota dynamics in olives across seasons or locations in the United States. We explored the composition and spatiotemporal patterns of the olive-associated microbial communities and specificity in two niches (rhizosphere and root endosphere), seasons (spring, summer, and fall), and domains (bacteria and fungi) in the microbiome of the olive cultivar Arbequina across three olive orchards in Texas. Phylum Proteobacteria, followed by Actinobacteriota, dominated the bacterial populations in the rhizosphere and endosphere. Rubrobacter and Actinophytocola were dominant taxa in the rhizosphere and root endosphere at the genus level. Among fungal communities, phylum Ascomycota was prevalent in the rhizosphere and endosphere, while members of the Chaetomiaceae family outnumbered other taxa in the root endosphere. As per the alpha diversity indices, the rhizosphere at Moulton showed much higher richness and diversity than other places, which predicted a significant difference in rhizosphere between locations for bacterial diversity and richness. There was no significant variation in the bacterial diversity in the niches and the fungal diversity within the root endosphere between locations. Beta diversity analysis confirmed the effect of compartments-in influencing community differences. Microbial diversity was apparent within the endosphere and rhizosphere. The seasons influenced only the rhizosphere fungal diversity, contrasting the bacterial diversity in either niche. The research provided a comprehensive overview of the microbial diversity in olive trees' rhizosphere and root endosphere. The abundance and composition of OTUs associated with the rhizosphere soil of Arbequina suggest its role as a source reservoir in defining the potential endophytes.

Protean Drainage Patterns of the Left Renal Vein: A Cadaveric and Retrospective Clinical Study on the Surgical Implications and Technical Feasibility.

BACKGROUND: The diverse drainage patterns of the left renal vein (LRV), often with asymptomatic congenital anomalies, present considerable challenges in renal and retroperitoneal surgical contexts. The potential for significant bleeding and subsequent renal compromise upon vascular injury highlights the need for increased surgical awareness. OBJECTIVE: This study investigates the LRV's variable anatomical drainage patterns and morphometry. It also evaluates the embryological factors contributing to these variations and discusses their surgical implications and technical considerations. METHODS: Anatomical dissections were conducted on 21 adult human cadavers within the Department of Anatomy. Concurrently, a retrospective analysis was conducted on 15 patients who underwent various retroperitoneal surgical interventions in the Urology Department. Demographic variables and intraoperative findings were recorded and analyzed. RESULTS: Dissection analysis predominantly identified preaortic LRVs in 18 cadavers. Notable anatomical variations included a circumaortic left renal vein (CLRV), a delayed preaortic confluence of extrahilar duo LRVs, and an extrahilar tetramerous confluence with a retroiliac topography. The majority of LRVs usually end in the inferior vena cava. However, an extrahilar tetramerous variant had an unusual drainage pathway. Out of 15 cases, three (20%) had a retroaortic left renal vein (RLRV). One patient with a nonfunctioning kidney had type 1 RLRV, and another patient with pelvic ureteric junction obstruction had type 4 retroiliac left renal vein (RILRV). In both of these patients, symptoms were relieved after surgery. In a young patient with left varicocele and microscopic hematuria who had type 2 RLRV, symptoms resolved spontaneously after a few months. CONCLUSION: A thorough understanding of the variable anatomical drainage patterns of the LRV is crucial for surgeons. Accurate preoperative identification can provide valuable insights, potentially leading to improved surgical outcomes in renal procedures.

Power-dependent study of the photothermal response of several alcoholic media with femtosecond laser-induced thermal lens.

We explore the photothermal response of methanol, ethylene glycol, and glycerol using the femtosecond laser-induced thermal lens spectroscopy (FTLS) technique. A mode mismatched pump-probe spectroscopic technique was utilized to analyze the influence of localized thermal heating on the photothermal response of solvents. The findings revealed a strong dependence on both the input pump power and the molecular characteristics of the solvents. At significantly high pump power, the excess heat load deposited to the solvent is found to be responsible for the induction of the convection currents in the heat transfer mechanisms. Our results highlight that the influence of pump power on photothermal and thermal lens characteristics is intricately linked to the natural drifting and heat transfer mechanisms of solvent molecules. The molecular motion and existing connective processes were correlated with the molecular characteristics of the samples. The present finding reveals that FTLS is a sensitive probe for comprehending the impact of input laser power, molecular structure, and intermolecular H bonding on the photothermal characteristics and thermo-optical properties of the alcoholic medium.

Association of anaemia with indoor air pollution among older Indian adult population: multilevel modelling analysis of nationally representative cross-sectional study.

INTRODUCTION: Anaemia is a disease of public health importance with multi-causal pathways. Previous literature suggests the role of indoor air pollution (IAP) on haemoglobin levels, but this has been studied less due to logistic constraints. A high proportion of the population in developing countries, including India, still depends on unclean fuel, which exacerbates IAP. The objective was to study the association between anaemia and IAP among the older Indian adult population (≥ 45 years) as per gender. METHODS: Our study analysed the nationally representative dataset of the Longitudinal Ageing Study in India (LASI 2017-18, Wave-1). We have documented the association of anaemia (outcome variable) with IAP (explanatory variable). To reduce the confounding effects of demographic and socioeconomic; health related and behavioural covariates; propensity score matching (PSM) was conducted. Nested multilevel regression modelling was conducted. States and union territories were categorised cross tabulated as low, middle and high as per anaemia and IAP exposure. P value < 0.05 was considered statistically significant. SATA version 17 was used for analysis. RESULTS: More than half (52.52%) of the participants were exposed to IAP (male (53.55%) > female (51.63%)). The odds of having anaemia was significantly 1.19 times higher (AOR 1.19 (1.09-1.31)) among participants using unclean/ solid fuel. The adjusted odds were significantly higher among participants exposed to pollution-generating sources (AOR 1.30; 1.18-1.43), and household indoor smoking (AOR 1.17 (1.07-1.29). The odds of having anaemia were significantly higher (AOR 1.26; 1.15-1.38) among participants exposed to IAP, which was higher in males (AOR 1.36; 1.15-1.61) than females (AOR 1.21; 1.08-1.35). Empowered Action Group (EAG) states like Uttar Pradesh, Chhattisgarh, Madhya Pradesh, Bihar had both high anaemia and IAP exposure. CONCLUSION: This study established the positive association of anaemia with indoor air pollution among older Indian adults through a nationally representative large dataset. The association was higher among men. Further research is recommended to understand detailed causation and to establish temporality. It is a high time to implement positive intervention nationally to decrease solid/ unclean fuel usage, vulnerable ventilation, indoor smoking, IAP and health hazards associated with these with more focused actions towards EAG states.

Observational evidence of changing cloud macro-physical properties under warming climate over the Indian summer monsoon region.

The cloud responses to global warming are captured in various global climate models with distinct inferences on changes in cloud vertical structure as function of surface warming. However, long term observational evidences are scarce to validate the model outputs. Here, we have studied the changes in radiosonde derived cloud macro-physical properties and their association with other atmospheric variables during the period 2000-2019 in response to warming climate over the Indian summer monsoon region. We have observed a statistically significant increase in the frequency of cloudy days (∼13 % decade-1), high-level clouds (HLCs ∼11 % decade-1) and simultaneous decrease in low-level clouds (LLCs ∼8 % decade-1) over the Indian region during the monsoon season. The multiple linear regression, principle component analyses and further correlation analyses suggest significant associations between cloud vertical structure variations and large-scale climate indicators, such as global warming and El Niño-Southern Oscillation. The vertical extension of the tropospheric column and the upward shift of clouds, attributed to global warming, explain the changes observed in both HLCs and LLCs. These results contribute to a deeper understanding of the dynamic interplay between global climate change and regional cloud dynamics, with implications for weather and climate modeling.

Lipo-polymeric nano-complexes for dermal delivery of a model protein.

Delivering macromolecules across the skin poses challenges due to the barrier properties of stratum corneum. Different strategies have been reported to cross this barrier, such as chemical penetration enhancers and physical methods like microneedles, sonophoresis, electroporation, laser ablation, etc. Herein, we explored a cationic lipo-polymeric nanocarrier to deliver a model protein across the skin. A cationic amphiphilic lipo-polymer was used to prepare blank nanoplexes, which were subsequently complexed with anionic fluorescein-tagged bovine serum albumin (FITC-BSA). Blank nanoplexes and FITC-BSA complexed nanoplexes showed sizes of 93.72 ± 5.8 (PDI-0.250) and 145.9 ± 3.2 nm (PDI-0.258), respectively, and zeta potentials of 25.6 ± 7.0 mV and 9.17 ± 1.20 mV. In vitro cell culture, and toxicity studies showed optimal use of these nanocarriers, with hemocompatibility data indicating non-toxicity. Ex vivo skin permeation analysis showed a skin permeation rate of 33% after 24 h. The optimized formulation was loaded in a carbopol-based gel that exhibits non-Newtonian flow characteristics with shear-thinning behavior and variable thixotropy. The nanoplexes delivered via gel demonstrated skin permeation of 57% after 24 h in mice skin ex vivo. In vivo skin toxicity testing confirmed the low toxicity profile of these nanocarriers. These results are promising for the transdermal/dermal delivery of macromolecules, such as protein therapeutics, using nanoplexes.

An Updated Canvas of the RFC1-mediated CANVAS (Cerebellar Ataxia, Neuropathy and Vestibular Areflexia Syndrome).

Proliferation of specific nucleotide sequences within the coding and non-coding regions of numerous genes has been implicated in approximately 40 neurodegenerative disorders. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), a neurodegenerative disorder, is distinguished by a pathological triad of sensory neuropathy, bilateral vestibular areflexia and cerebellar impairments. It manifests in adults gradually and is autosomal recessive and multi-system ataxia. Predominantly, CANVAS is associated with biallelic AAGGG repeat expansions in intron 2 of the RFC1 gene. Although various motifs have been identified, only a subset induces pathological consequences, by forming stable secondary structures that disrupt gene functions both in vitro and in vivo. The pathogenesis of CANVAS remains a subject of intensive research, yet its precise mechanisms remain elusive. Herein, we aim to comprehensively review the epidemiology, clinical ramifications, molecular mechanisms, genetics, and potential therapeutics in light of the current findings, extending an overview of the most significant research on CANVAS.

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS-induced colitis in a murine model.

The excretory-secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30-150-nm-sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto-lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV-treated macrophages. Due to this, both macro-autophagy and caspase-linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT-mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV-mediated immune suppression revealed that the EV can protect the mice from DSS-induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential.

Isomeric and rotational effects in the chemi-ionisation of 1,2-dibromoethene with metastable neon atoms.

The specific geometry of a molecule can have a pronounced influence on its chemical reactivity. However, experimental data on reactions of individual molecular isomers are still sparse because they are often difficult to separate and frequently interconvert into one another under ambient conditions. Here, we employ a novel crossed-beam experiment featuring an electrostatically controlled molecular beam combined with a source for radicals and metastables to spatially separate the cis and trans stereoisomers as well as individual rotational states of 1,2-dibromoethene and study their specific reactivities in the chemi-ionisation reaction with excited neon atoms. The experiments reveal pronounced isomeric and rotational specificities in the rates and product branching ratios of the reaction. The present study underlines the importance and combined role of molecular geometry and of rotational motion in the dynamics of chemi-ionisation reactions.

Technical and Anatomical Aspects of Retroperitoneoscopic Renal Surgery: A Summary of Tribulations and Resolutions Encountered at a Tertiary Care Institute of North India.

INTRODUCTION: Kidneys are a retroperitoneal organ but the widely practiced laparoscopic approach to renal surgery is transperitoneal due to the advantages of greater working space at the cost of entering the peritoneal cavity, risk of injury to intraperitoneal organs, and the increased risk of postoperative bowel complications. The classic open approach to kidney procedures has been the flank approach without violating the peritoneal cavity instead of the retroperitoneal approach to renal surgery with the advantages of direct access to the renal hilum, especially the renal artery. Being a technically challenging procedure, the retroperitoneoscopic approach is less practiced and needs an experienced surgical team. Through this study, we have tried to unveil the myths and illustrate the exact position of ports, which is the decisive initial step in retroperitoneoscopic surgery. MATERIAL AND METHODS: This retrospective study was conducted at a developing tertiary center in northern India with novice staff mainly to determine the technical and anatomical caveats pertaining to the retroperitoneoscopic approach for renal surgeries, the challenges faced, and their resolutions. The decision for the site of incision for primary or camera port was taken only after a proper anatomical study of the cadavers and ongoing retroperitoneal surgical experience while treating various patients suffering from renal diseases. The study comprised eight patients, during the period from June 2023 to March 2024. Various parameters, such as demographic variables, diagnosis, mean operative time, estimated blood loss, technical difficulties encountered and their resolution, complications, and reasons for conversion were studied. A total of 15 cadavers were dissected during the above time period to study finer anatomical details of port positioning and other details. RESULTS: After an elaborate study of 15 cadavers and thereafter performing surgery on eight patients during the above time period, surgery was successfully performed on six patients, and two patients needed conversion to open procedure due to dense adhesions and non-progression while complications occurred in two patients (peritoneal rent and renal vein injury), which were managed laparoscopically. CONCLUSION:  Nonetheless, restrictions of surgical space make retroperitoneoscopic space a challenging procedure but with elaborate experience, which we gained through cadaveric study, and surgical results obtained during the initial few cases such as the exact site of the primary port and technical intricacies, and handling of complications if and when faced, we hope our study will certainly make retroperitoneal space more amicable to urologists.

Acetaminophen induces mitochondrial apoptosis through proteasome dysfunctions.

Acetaminophen is a known antipyretic and non-opioid analgesic for mild pain and fever. Numerous studies uncover their hidden chemotherapeutics applications, including chronic cancer pain management. Acetaminophen also represents an anti-proliferative effect in some cancer cells. Few studies also suggest that the use of Acetaminophen can trigger apoptosis and impede cellular growth. However, Acetaminophen's molecular potential and precise mechanism against improper cellular proliferation and use as an effective anti-proliferative agent still need to be better understood. Here, our current findings show that Acetaminophen induces proteasomal dysfunctions, resulting in aberrant protein accumulation and mitochondrial abnormalities, and consequently induces cell apoptosis. We observed that the Acetaminophen treatment leads to improper aggregation of ubiquitylated expanded polyglutamine proteins, which may be due to the dysfunctions of proteasome activities. Our in-silico analysis suggests the interaction of Acetaminophen and proteasome. Furthermore, we demonstrated the accumulation of proteasome substrates and the depletion of proteasome activities after treating Acetaminophen in cells. Acetaminophen induces proteasome dysfunctions and mitochondrial abnormalities, leading to pro-apoptotic morphological changes and apoptosis successively. These results suggest that Acetaminophen can induce cell death and may retain a promising anti-proliferative effect. These observations can open new possible molecular strategies in the near future for developing and designing specific and effective proteasome inhibitors, which can be helpful in conjugation with other anti-tumor drugs for their better efficiency.

Proteostasis in neurodegenerative diseases.

Proteostasis is essential for normal function of proteins and vital for cellular health and survival. Proteostasis encompasses all stages in the "life" of a protein, that is, from translation to functional performance and, ultimately, to degradation. Proteins need native conformations for function and in the presence of multiple types of stress, their misfolding and aggregation can occur. A coordinated network of proteins is at the core of proteostasis in cells. Among these, chaperones are required for maintaining the integrity of protein conformations by preventing misfolding and aggregation and guide those with abnormal conformation to degradation. The ubiquitin-proteasome system (UPS) and autophagy are major cellular pathways for degrading proteins. Although failure or decreased functioning of components of this network can lead to proteotoxicity and disease, like neuron degenerative diseases, underlying factors are not completely understood. Accumulating misfolded and aggregated proteins are considered major pathomechanisms of neurodegeneration. In this chapter, we have described the components of three major branches required for proteostasis-chaperones, UPS and autophagy, the mechanistic basis of their function, and their potential for protection against various neurodegenerative conditions, like Alzheimer's, Parkinson's, and Huntington's disease. The modulation of various proteostasis network proteins, like chaperones, E3 ubiquitin ligases, proteasome, and autophagy-associated proteins as therapeutic targets by small molecules as well as new and unconventional approaches, shows promise.

Sex Distributions in Non-ABCA4 Autosomal Macular Dystrophies.

Purpose: We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies. Methods: We searched the electronic patient records of our large inherited retinal disease cohort, quantifying numbers of males and females with the more common (non-ABCA4) inherited macular dystrophies (associated with BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3). BEST1 cases were subdivided into typical autosomal dominant and recessive disease. For PRPH2, only patients with variants at codons 172 or 142 were included. Recessive PROM1 and recessive RP1L1 cases were excluded because these variants give a more widespread or peripheral degeneration. The proportion of females was calculated for each condition; two-tailed binomial testing was performed. Where a significant imbalance was found, previously published cohorts were also explored. Results: Of 325 patients included, numbers for BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3 were 152, 35, 30, 50, 14, and 44, respectively. For autosomal dominant Best disease (n = 115), there were fewer females (38%; 95% confidence interval [CI], 29-48%; P = 0.015). For EFEMP1-associated disease (n = 35), there were significantly more females (77%; 95% CI, 60%-90%; P = 0.0019). No significant imbalances were seen for the other genes. When pooling our cohort with previous large dominant Best disease cohorts, the proportion of females was 37% (95% CI, 31%-43%; P = 1.2 × 10-5). Pooling previously published EFEMP1-cases with ours yielded an overall female proportion of 62% (95% CI, 54%-69%; P = 0.0023). Conclusions: This exploratory study found significant sex imbalances in two autosomal macular dystrophies, suggesting that sex could be a modifier. Our findings invite replication in further cohorts and the investigation of potential mechanisms.

Baseline findings of a multicentric ambispective cohort study (2021-2022) among hospitalised mucormycosis patients in India.

In India, the incidence of mucormycosis reached high levels during 2021-2022, coinciding with the COVID-19 pandemic. In response to this, we established a multicentric ambispective cohort of patients hospitalised with mucormycosis across India. In this paper, we report their baseline profile, clinical characteristics and outcomes at discharge. Patients hospitalized for mucormycosis during March-July 2021 were included. Mucormycosis was diagnosed based on mycological confirmation on direct microscopy (KOH/Calcofluor white stain), culture, histopathology, or supportive evidence from endoscopy or imaging. After consent, trained data collectors used medical records and telephonic interviews to capture data in a pre-tested structured questionnaire. At baseline, we recruited 686 patients from 26 study hospitals, of whom 72.3% were males, 78% had a prior history of diabetes, 53.2% had a history of corticosteroid treatment, and 80% were associated with COVID-19. Pain, numbness or swelling of the face were the commonest symptoms (73.3%). Liposomal Amphotericin B was the commonest drug formulation used (67.1%), and endoscopic sinus surgery was the most common surgical procedure (73.6%). At discharge, the disease was stable in 43.3%, in regression for 29.9% but 9.6% died during hospitalization. Among survivors, commonly reported disabilities included facial disfigurement (18.4%) and difficulties in chewing/swallowing (17.8%). Though the risk of mortality was only 1 in 10, the disability due to the disease was very high. This cohort study could enhance our understanding of the disease's clinical progression and help frame standard treatment guidelines.

Aneurysms of Aortic Sinus of Valsalva Dissecting through the Interventricular Septum With Rupture into the Left Ventricle: Case Series and Literature Review.

Aneurysm of Aortic sinus of Valsalva (ASOV) dissecting into the interventricular septum (IVS) and rupturing into the left ventricle (LV) is a rare clinical diagnosis. Systemic inflammatory diseases like tuberculosis can aggravate this condition. We describe three cases of ASOV dissecting into the IVS and rupturing into the LV. All three patients underwent surgical intervention; two had a successful outcome. A literature review was conducted and19 previously reported cases were studied. The extent and direction of septal dissection determined the associated cardiac valvular and rhythm problems. Patch closure of the mouth of the aneurysm is the surgical method of choice. In the presence of multiple sinus tracts or if there is recurrence after surgical closure, aortic sinus or root replacement techniques have better outcomes.

Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities.

SCLC is refractory to conventional therapies; targeted therapies and immunological checkpoint inhibitor (ICI) molecules have prolonged survival only marginally. In addition, ICIs help only a subgroup of SCLC patients. Different types of kinases play pivotal roles in therapeutics-driven cellular functions. Therefore, there is a significant need to understand the roles of kinases in regulating therapeutic responses, acknowledge the existing knowledge gaps, and discuss future directions for improved therapeutics for recalcitrant SCLC. Here, we extensively review the effect of dysregulated kinases in SCLC. We further discuss the pharmacological inhibitors of kinases used in targeted therapies for recalcitrant SCLC. We also describe the role of kinases in the ICI-mediated activation of antitumor immune responses. Finally, we summarize the clinical trials evaluating the potential of kinase inhibitors and ICIs. This review overviews dysregulated kinases in SCLC and summarizes their potential as targeted therapeutic agents. We also discuss their clinical efficacy in enhancing anticancer responses mediated by ICIs.

Nanosensor based approaches for quantitative detection of heparin.

Heparin, being a widely employed anticoagulant in numerus clinical complications, requires strict quantification and qualitative screening to ensure the safety of patients from potential threat of thrombocytopenia. However, the intricacy of heparin's chemical structures and low abundance hinders the precise monitoring of its level and quality in clinical settings. Conventional laboratory assays have limitations in sensitivity and specificity, necessitating the development of innovative approaches. In this context, nanosensors emerged as a promising solution due to enhanced sensitivity, selectivity, and ability to detect heparin even at low concentrations. This review delves into a range of sensing approaches including colorimetric, fluorometric, surface-enhanced Raman spectroscopy, and electrochemical techniques using different types of nanomaterials, thus providing insights of its principles, capabilities, and limitations. Moreover, integration of smart-phone with nanosensors for point of care diagnostics has also been explored. Additionally, recent advances in nanopore technologies, artificial intelligence (AI) and machine learning (ML) have been discussed offering specificity against contaminants present in heparin to ensure its quality. By consolidating current knowledge and highlighting the potential of nanosensors, this review aims to contribute to the advancement of efficient, reliable, and economical heparin detection methods providing improved patient care.

Targeting chemokine-receptor mediated molecular signaling by ethnopharmacological approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Infection and inflammation are critical to global human health status and the goal of current pharmacological interventions intends formulating medications/preventives as a measure to deal with this situation. Chemokines and their cognate receptors are major regulatory molecules in many of these ailments. Natural products have been a keen source to the drug development industry, every year contributing significantly to the growing list of FDA approved drugs. A multiverse of natural resource is employed as a part of curative regimen in folk/traditional/ethnomedicine which can be employed to discover, repurpose, and design potent medications for the diseases of clinical concern. AIM OF THE STUDY: This review aims to systematically document the ethnopharmacologically active agents targeting the infectious-inflammatory diseases through the chemokine-receptor nexus. MATERIALS AND METHODS: Articles related to chemokine/receptor modulating ethnopharmacological anti-inflammatory, anti-infectious natural sources, bioactive compounds, and formulations have been examined with special emphasis on women related diseases. The available literature has been thoroughly scrutinized for the application of traditional medicines in chemokine associated experimental methods, their regulatory outcomes, and pertinence to women's health wherever applicable. Moreover, the potential traditional regimens under clinical trials have been critically assessed. RESULTS: A systematic and comprehensive review on the chemokine-receptor targeting ethnopharmaceutics from the available literature has been provided. The article discusses the implication of traditional medicine in the chemokine system dynamics in diverse infectious-inflammatory disorders such as cardiovascular diseases, allergic diseases, inflammatory diseases, neuroinflammation, and cancer. On this note, critical evaluation of the available data surfaced multiple diseases prevalent in women such as osteoporosis, rheumatoid arthritis, breast cancer, cervical cancer and urinary tract infection. Currently there is no available literature highlighting chemokine-receptor targeting using traditional medicinal approach from women's health perspective. Moreover, despite being potent in vitro and in vivo setups there remains a gap in clinical translation of these formulations, which needs to be strategically and scientifically addressed to pave the way for their successful industrial translation. CONCLUSIONS: The review provides an optimistic global perspective towards the applicability of ethnopharmacology in chemokine-receptor regulated infectious and inflammatory diseases with special emphasis on ailments prevalent in women, consecutively addressing their current status of clinical translation and future directions.

4-(Benzyloxy)phenol-induced p53 exhibits antimycobacterial response triggering phagosome-lysosome fusion through ROS-dependent intracellular Ca2+ pathway in THP-1 cells.

Drug-resistant tuberculosis (TB) outbreak has emerged as a global public health crisis. Therefore, new and innovative therapeutic options like host-directed therapies (HDTs) through novel modulators are urgently required to overcome the challenges associated with TB. In the present study, we have investigated the anti-mycobacterial effect of 4-(Benzyloxy)phenol. Cell-viability assay asserted that 50 µM of 4-(Benzyloxy)phenol was not cytotoxic to phorbol 12-myristate 13-acetate (PMA) differentiated THP-1 (dTHP-1) cells. It was observed that 4-(Benzyloxy)phenol activates p53 expression by hindering its association with KDM1A. Increased ROS, intracellular Ca2+ and phagosome-lysosome fusion, were also observed upon 4-(Benzyloxy)phenol treatment. 4-(Benzyloxy)phenol mediated killing of intracellular mycobacteria was abrogated in the presence of specific inhibitors of ROS, Ca2+ and phagosome-lysosome fusion like NAC, BAPTA-AM, and W7, respectively. We further demonstrate that 4-(Benzyloxy)phenol mediated enhanced ROS production is mediated by acetylation of p53. Blocking of p53 acetylation by Pifithrin-α (PFT- α) enhanced intracellular mycobacterial growth by blocking the mycobactericidal effect of 4-(Benzyloxy)phenol. Altogether, the results showed that 4-(Benzyloxy)phenol executed its anti-mycobacterial effect by modulating p53-mediated ROS production to regulate phagosome-lysosome fusion through Ca2+ production.